Ribozyme treatment of diseases or conditions related to levels of NF-kappaB

ABSTRACT

Enzymatic RNA molecules which cleave rel A mRNA.

RELATED APPLICATIONS

[0001] This application is a continuation-in-part of Stinchcomb et al.,“Method and Composition for Treatment of Restenosis and Cancer UsingRibozymes,” filed May 18, 1994, U.S. Ser. No. 08/245,466 which is acontinuation-in-part of Draper, “Method and Reagent for Treatment of aStenotic Condition”, filed Dec. 7, 1992, U.S. Ser. No. 07/987,132, bothhereby incorporated by reference herein.

FIELD OF THE INVENTION

[0002] The present invention relates to therapeutic compositions andmethods for the treatment or diagnosis of diseases or conditions relatedto NF-κB levels, such as restenosis, rheumatoid arthritis, asthma,inflammatory or autoimmune disorders and transplant rejection.

BACKGROUND OF THE INVENTION

[0003] The following is a brief description of the physiological role ofNF-κB. The discussion is not meant to be complete and is provided onlyfor understanding of the invention that follows. This summary is not anadmission that any of the work described below is prior art to theclaimed invention.

[0004] The nuclear DNA-binding activity, NF-κB, was first identified asa factor that binds and activates the immunoglobulin K light chainenhancer in B cells. NF-κB now is known to activate transcription of avariety of other cellular genes (e.g., cytokines, adhesion proteins,oncogenes and viral proteins) in response to a variety of stimuli (e.g.,phorbol esters, mitogens, cytokines and oxidative stress). In addition,molecular and biochemical characterization of NF-κB has shown that theactivity is due to a homodimer or heterodimer of a family of DNA bindingsubunits. Each subunit bears a stretch of 300 amino acids that ishomologous to the oncogene, v-rel. The activity first described as NF-κBis a heterodimer of p49 or p50 with p65. The p49 and p50 subunits ofNF-κB (encoded by the nf-κB2 or nf-κB1 genes, respectively) aregenerated from the precursors NF-κB1 (p105) or NF-κB2 (p100). The p65subunit of NF-κB (now termed Rel A) is encoded by the rel A locus.

[0005] The roles of each specific transcription-activating complex noware being elucidated in cells (N. D. Perkins, et al., 1992 Proc. Natl.Acad. Sci USA 89, 1529-1533). For instance, the heterodimer of NF-κB1and Rel A (p50/p65) activates transcription of the promoter for theadhesion molecule, VCAM-1, while NF-κB2/RelA heterodimers (p49/p65)actually inhibit transcription (H. B. Shu, et al., Mol. Cell. Biol. 13,6283-6289 (1993)). Conversely, heterodimers of NF-κB2/RelA (p49/p65) actwith Tat-I to activate transcription of the HIV genome, whileNF-κB1/RelA (p50/p65) heterodimers have little effect (J. Liu, N. D.Perkins, R. M. Schmid, G. J. Nabel, J. Virol. 1992 66, 3883-3887).Similarly, blocking rel A gene expression with antisenseoligonucleotides specifically blocks embryonic stem cell adhesion;blocking NF-κB1 gene expression with antisense oligonucleotides had noeffect on cellular adhesion (Narayanan et al., 1993 Mol. Cell. Biol. 13,3802-3810). Thus, the promiscuous role initially assigned to NF-κB intranscriptional activation (M. J. Lenardo, D. Baltimore, 1989 Cell 58,227-229) represents the sum of the activities of the rel family ofDNA-binding proteins. This conclusion is supported by recent transgenic“knock-out” mice of individual members of the rel family. Such“knock-outs” show few developmental defects, suggesting that essentialtranscriptional activation functions can be performed by more than onemember of the rel family.

[0006] A number of specific inhibitors of NF-κB function in cells exist,including treatment with phosphorothioate antisense oliogonucleotide,treatment with double-stranded NF-κB binding sites, and over expressionof the natural inhibitor MAD-3 (an IκB family member). These agents havebeen used to show that NF-κB is required for induction of a number ofmolecules involved in inflammation, as described below.

[0007] NF-κB is required for phorbol ester-mediated induction of IL-6(I. Kitajima, et al., Science 258, 1792-5 (1992)) and IL-8 (Kunsch andRosen, 1993 Mol. Cell. Biol. 13, 6137-46).

[0008] NF-κB is required for induction of the adhesion molecules ICAM-1(Eck, et al., 1993 Mol. Cell. Biol. 13, 6530-6536), VCAM-1 (Shu et al.,supra), and E-selectin (Read, et al., 1994 J. Exp. Med. 179, 503-512) onendothelial cells.

[0009] NF-κB is involved in the induction of the integrin subunit, CD18,and other adhesive properties of leukocytes (Eck et al., 1993 supra).

[0010] The above studies suggest that NF-κB is integrally involved inthe induction of cytokines and adhesion molecules by inflammatorymediators. Two recent papers point to another connection between NF-κBand inflammation: glucocorticoids may exert their anti-inflammatoryeffects by inhibiting NF-κB. The glucocorticoid receptor and p65 bothact at NF-κB binding sites in the ICAM-1 promoter (van de Stolpe, etal., 1994 J. Biol. Chem. 269, 6185-6192). Glucocorticoid receptorinhibits NF-κB-mediated induction of IL-6 (Ray and Prefontaine, 1994Proc. Natl Acad. Sci USA 91, 752-756). Conversely, overexpression of p65inhibits glucocorticoid induction of the mouse mammary tumor viruspromoter. Finally, protein cross-linking and co-immunoprecipitationexperiments demonstrated direct physical interaction between p65 and theglucocorticoid receptor (Id.).

SUMMARY OF THE INVENTION

[0011] This invention relates to ribozymes, or enzymatic RNA molecules,directed to cleave mRNA species encoding Rel A protein (p65). Inparticular, applicant describes the selection and function of ribozymescapable of cleaving this RNA and their use to reduce activity of NF-κBin various tissues to treat the diseases discussed herein. Suchribozymes are also useful for diagnostic applications.

[0012] Ribozymes that cleave rel A mRNA represent a novel therapeuticapproach to inflammatory or autoimmune disorders. Antisense DNAmolecules have been described that block NF-κB activity. See Narayananet al., supra. However, ribozymes may show greater perdurance or lowereffective doses than antisense molecules due to their catalyticproperties and their inherent secondary and tertiary structures. Suchribozymes, with their catalytic activity and increased site specificity(as described below), represent more potent and safe therapeuticmolecules than antisense oligonucleotides.

[0013] Applicant indicates that these ribozymes are able to inhibit theactivity of NF-κB and that the catalytic activity of the ribozymes isrequired for their inhibitory effect. Those of ordinary skill in theart, will find that it is clear from the examples described that otherribozymes that cleave rel A encoding mRNAs may be readily designed andare within the invention.

[0014] Six basic varieties of naturally-occurring enzymatic RNAs areknown presently. Each can catalyze the hydrolysis of RNA phosphodiesterbonds in trans (and thus can cleave other RNA molecules) underphysiological conditions. Table I summarizes some of the characteristicsof these ribozymes. In general, enzymatic nucleic acids act by firstbinding to a target RNA. Such binding occurs through the target bindingportion of a enzymatic nucleic acid which is held in close proximity toan enzymatic portion of the molecule that acts to cleave the target RNA.Thus, the enzymatic nucleic acid first recognizes and then binds atarget RNA through complementary base-pairing, and once bound to thecorrect site, acts enzymatically to cut the target RNA. Strategiccleavage of such a target RNA will destroy its ability to directsynthesis of an encoded protein. After an enzymatic nucleic acid hasbound and cleaved its RNA target, it is released from that RNA to searchfor another target and can repeatedly bind and cleave new targets.

[0015] The enzymatic nature of a ribozyme is advantageous over othertechnologies, such as antisense technology (where a nucleic acidmolecule simply binds to a nucleic acid target to block its translation)since the concentration of ribozyme necessary to affect a therapeutictreatment is lower than that of an antisense oligonucleotide. Thisadvantage reflects the ability of the ribozyme to act enzymatically.Thus, a single ribozyme molecule is able to cleave many molecules oftarget RNA. In addition, the ribozyme is a highly specific inhibitor,with the specificity of inhibition depending not only on the basepairing mechanism of binding to the target RNA, but also on themechanism of target RNA cleavage. Single mismatches, orbase-substitutions, near the site of cleavage can completely eliminatecatalytic activity of a ribozyme. Similar mismatches in antisensemolecules do not prevent their action (Woolf, T. M., et al., 1992, Proc.Natl. Acad. Sci. USA, 89, 7305-7309). Thus, the specificity of action ofa ribozyme is greater than that of an antisense oligonucleotide bindingthe same RNA site.

[0016] In preferred embodiments of this invention, the enzymatic nucleicacid molecule is formed in a hammerhead or hairpin motif, but may alsobe formed in the motif of a hepatitis delta virus, group I intron orRNaseP RNA (in association with an RNA guide sequence) or Neurospora VSRNA. Examples of such hammerhead motifs are described by Rossi et al.,1992, Aids Research and Human Retroviruses, 8, 183, of hairpin motifs byHampel et al., “RNA Catalyst for Cleaving Specific RNA Sequences,” filedSep. 20, 1989, which is a continuation-in-part of U.S. Ser. No.07/247,100 filed Sep. 20, 1988, Hampel and Tritz, 1989, Biochemistry,28, 4929, and Hampel et al., 1990, Nucleic Acids Res.earch, 18,299, andan example of the hepatitis delta virus motif is described by Perrottaand Been, 1992, Biochemistry, 31, 16, of the RNaseP motif byGuerrier-Takada et al., 1983, Cell, 35, 849, Neurospora VS RNA ribozymemotif is described by Collins (Saville and Collins, 1990 Cell 61,685-696; Saville and Collins, 1991 Proc. Natl. Acad. Sci. USA 88,8826-8830; Collins and Olive, 1993 Biochemistry 32, 2795-2799) and ofthe Group I intron by Cech et al., U.S. Pat. No. 4,987,071. Thesespecific motifs are not limiting in the invention and those skilled inthe art will recognize that all that is important in an enzymaticnucleic acid molecule of this invention is that it has a specificsubstrate binding site which is complementary to one or more of thetarget gene RNA regions, and that it have nucleotide sequences within orsurrounding that substrate binding site which impart an RNA cleavingactivity to the molecule.

[0017] The invention provides a method for producing a class ofenzymatic cleaving agents which exhibit a high degree of specificity forthe RNA of a desired target. The enzymatic nucleic acid molecule ispreferably targeted to a highly conserved sequence region of a targetRel A encoding mRNA such that specific treatment of a disease orcondition can be provided with either one or several enzymatic nucleicacids. Such enzymatic nucleic acid molecules can be deliveredexogenously to specific cells as required. Alternatively, the ribozymescan be expressed from DNA vectors that are delivered to specific cells.

[0018] Synthesis of nucleic acids greater than 100 nucleotides in lengthis difficult using automated methods, and the therapeutic cost of suchmolecules is prohibitive. In this invention, small enzymatic nucleicacid motifs (e.g., of the hammerhead or the hairpin structure) are usedfor exogenous delivery. The simple structure of these moleculesincreases the ability of the enzymatic nucleic acid to invade targetedregions of the mRNA structure. However, these catalytic RNA moleculescan also be expressed within cells from eukaryotic promoters (e.g.,Scanlon, K. J., et al., 1991, Proc. Natl. Acad. Sci. USA, 88, 10591-5;Kashani-Sabet, M., et al., 1992, Antisense Res. Dev., 2, 3-15; Dropulic,B., et al., 1992, J. Virol, 66, 1432-41; Weerasinghe, M., et al., 1991,J. Virol, 65, 5531-4; Ojwang, J. O., et al., 1992, Proc. Natl. Acad.Sci. USA, 89, 10802-6; Chen, C. J., et al., 1992, Nucleic Acids Res.,20, 4581-9; Sarver, H., et al., 1990, Science, 247, 1222-1225)). Thoseskilled in the art realize that any ribozyme can be expressed ineukaryotic cells from the appropriate DNA vector. The activity of suchribozymes can be augmented by their release from the primary transcriptby a second ribozyme (Draper et al., PCT WO93/23569, and Sullivan etal., PCT WO94/02595, both hereby incorporated in their totality byreference herein; Ohkawa, J., et al., 1992, Nucleic Acids Symp. Ser.,27, 15-6; Taira, K., et al., 1991, Nucleic Acids Res., 19, 5125-30;Ventura, M., et al., 1993, Nucleic Acids Res., 21, 3249-55).

[0019] Inflammatory mediators such as lipopolysaccharide (LPS),interleukin-1 (IL-1) or tumor necrosis factor-a (TNF-α) act on cells byinducing transcription of a number of secondary mediators, includingother cytokines and adhesion molecules. In many cases, this geneactivation is known to be mediated by the transcriptional regulator,NF-κB. One subunit of NF-κB, the relA gene product (termed RelA or p65)is implicated specifically in the induction of inflammatory responses.Ribozyme therapy, due to its exquisite specificity, is particularlywell-suited to target intracellular factors that contribute to diseasepathology. Thus, ribozymes that cleave mRNA encoded by rel A mayrepresent novel therapeutics for the treatment of inflammatory andautoimmune disorders.

[0020] Thus, in a first aspect, the invention features ribozymes thatinhibit RelA production. These chemically or enzymatically synthesizedRNA molecules contain substrate binding domains that bind to accessibleregions of their target mRNAs. The RNA molecules also contain domainsthat catalyze the cleavage of RNA. The RNA molecules are preferablyribozymes of the hammerhead or hairpin motif. Upon binding, theribozymes cleave the target RelA encoding mRNAs, preventing translationand p65 protein accumulation. In the absence of the expression of thetarget gene, a therapeutic effect may be observed.

[0021] By “inhibit” is meant that the activity or level of RelA encodingmRNA is reduced below that observed in the absense of the ribozyme, andpreferably is below that level observed in the presence of an inactiveRNA molecule able to bind to the same site on the mRNA, but unable tocleave that RNA.

[0022] Such ribozymes are useful for the prevention of the diseases andconditions discussed above, and any other diseases or conditions thatare related to the level of NF-κB activity in a cell or tissue. By“related” is meant that the inhibition of relA mRNA and thus reductionin the level of NF-κB activity will relieve to some extent the symptomsof the disease or condition.

[0023] Ribozymes are added directly, or can be complexed with cationiclipids, packaged within liposomes, or otherwise delivered to targetcells. The RNA or RNA complexes can be locally administered to relevanttissues ex vivo, or in vivo through injection or the use of a catheter,infusion pump or stent, with or without their incorporation inbiopolymers. In preferred embodiments, the ribozymes have binding armswhich are complementary to the sequences in Tables II, III, VI-VII.Examples of such ribozymes are shown in Tables IV-VII. Examples of suchribozymes consist essentially of sequences defined in these Tables. By“consists essentially of” is meant that the active ribozyme contains anenzymatic center equivalent to those in the examples, and binding armsable to bind mRNA such that cleavage at the target site occurs. Othersequences may be present which do not interfere with such cleavage.

[0024] In another aspect of the invention, ribozymes that cleave targetmolecules and inhibit NF-κB activity are expressed from transcriptionunits inserted into DNA, RNA, or viral vectors. Preferably, therecombinant vectors capable of expressing the ribozymes are locallydelivered as described above, and transiently persist in target cells.Once expressed, the ribozymes cleave the target mRNA. The recombinantvectors are preferably DNA plasmids or adenovirus vectors. However,other mammalian cell vectors that direct the expression of RNA may beused for this purpose.

[0025] Other features and advantages of the invention will be apparentfrom the following description of the preferred embodiments thereof, andfrom the claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] The drawings will first briefly be described.

DRAWINGS

[0027]FIG. 1 is a diagrammatic representation of the hammerhead ribozymedomain known in the art.

[0028]FIG. 2a is a diagrammatic representation of the hammerheadribozyme domain known in the art;

[0029]FIG. 2b is a diagrammatic representation of the hammerheadribozyme as divided by Uhlenbeck (1987, Nature, 327, 596-600) into asubstrate and enzyme portion;

[0030]FIG. 2c is a similar diagram showing the hammerhead divided byHaseloff and Gerlach (1988, Nature, 334, 585-591) into two portions; and

[0031]FIG. 2d is a similar diagram showing the hammerhead divided byJeffries and Symons (1989, Nucl. Acids. Res., 17, 1371-1371) into twoportions.

[0032]FIG. 3 is a representation of the general structure of the hairpinribozyme domain known in the art.

[0033]FIG. 4 is a representation of the general structure of thehepatitis delta virus ribozyme domain known in the art.

[0034]FIG. 5 is a representation of the general structure of the VS RNAribozyme domain known in the art.

[0035]FIG. 6 is a schematic representation of an RNAseH accessibilityassay. Specifically, the left side of FIG. 6 is a diagram ofcomplementary DNA oligonucleotides bound to accessible sites on thetarget RNA. Complementary DNA oligonucleotides are represented by broadlines labeled A, B, and C. Target RNA is represented by the thin,twisted line. The right side of FIG. 6 is a schematic of a gelseparation of uncut target RNA from a cleaved target RNA. Detection oftarget RNA is by autoradiography of body-labeled, T7 transcript. Thebands common to each lane represent uncleaved target RNA; the bandsunique to each lane represent the cleaved products.

[0036] Ribozymes

[0037] Ribozymes of this invention block to some extent NF-κB expressionand can be used to treat disease or diagnose such disease. Ribozymeswill be delivered to cells in culture and to cells or tissues in animalmodels of restenosis, transplant rejection and rheumatoid arthritis.Ribozyme cleavage of relA mRNA in these systems may prevent inflammatorycell function and alleviate disease symptoms.

[0038] Target Sites

[0039] Targets for useful ribozymes can be determined as disclosed inDraper et al supra, Sullivan et al., supra, as well as by Draper et al.,“Method and reagent for treatment of arthritic conditions U.S. Ser. No.08/152,487, filed Nov. 12, 1993, and hereby incorporated by referenceherein in totality. Rather than repeat the guidance provided in thosedocuments here, below are provided specific examples of such methods,not limiting to those in the art. Ribozymes to such targets are designedas described in those applications and synthesized to be tested in vitroand in vivo, as also described. Such ribozymes can also be optimized anddelivered as described therein. While specific examples to mouse andhuman RNA are provided, those in the art will recognize that theequivalent human RNA targets described can be used as described below.Thus, the same target may be used, but binding arms suitable fortargeting human RNA sequences are present in the ribozyme. Such targetsmay also be selected as described below.

[0040] The sequence of human and mouse relA mRNA can be screened foraccessible sites using a computer folding algorithm. Potentialhammerhead or hairpin ribozyme cleavage sites were identified. Thesesites are shown in Tables II, III, and VI-VII. (All sequences are 5′ to3′ in the tables.) While mouse and human sequences can be screened andribozymes thereafter designed, the human targetted sequences are of mostutility. However, as discussed in Stinchcomb et al. supra, mousetargetted ribozmes are useful to test efficacy of action of the ribozymeprior to testing in humans. The nucleotide base position is noted in theTables as that site to be cleaved by the designated type of ribozyme.(In Table II, lower case letters indicate positions that are notconserved between the Human and the Mouse relA sequences.)

[0041] Hammerhead ribozymes are designed that could bind and areindividually analyzed by computer folding (Jaeger, J. A., et al., 1989,Proc. Natl. Acad. Sci. USA, 86, 7706-7710) to assess whether, theribozyme sequences fold into the appropriate secondary structure. Thoseribozymes with unfavorable intramolecular interactions between thebinding arms and the catalytic core are eliminated from consideration.Varying binding arm lengths can be chosen to optimize activity.Generally, at least 5 bases on each arm are able to bind to, orotherwise interact with, the target RNA.

[0042] Referring to FIG. 6, mRNA is screened for accessible cleavagesites by the method described generally in Draper et al., WO/US93/04020hereby incorporated by reference herein. Briefly, DNA oligonucleotidesrepresenting potential hammerhead ribozyme cleavage sites aresynthesized. A polymerase chain reaction is used to generate a substratefor T7 RNA polymerase transcription from human or murine rel A cDNAclones. Labeled RNA transcripts are synthesized in vitro from the twotemplates. The oligonucleotides and the labeled transcripts areannealed, RNAseH is added and the mixtures are incubated for thedesignated times at 37° C. Reactions are stopped and RNA separated onsequencing polyacrylamide gels. The percentage of the substrate cleavedis determined by autoradiographic quantitation using a phosphor imagingsystem. From these data, hammerhead ribozyme sites are chosen as themost accessible.

[0043] Ribozymes of the hammerhead motif are designed to anneal tovarious sites in the mRNA message. The binding arms are complementary tothe target site sequences described above. The ribozymes are chemicallysynthesized. The method of synthesis used follows the procedure fornormal RNA synthesis as described in Usman, N.; Ogilvie, K. K.; Jiang,M. -Y.; Cedergren, R. J. 1987, J. Am. Chem. Soc., 109, 7845-7854 and inScaringe, S. A.; Franklyn, C.; Usman, N., 1990, Nucleic Acids Res., 18,5433-5441 and makes use of common nucleic acid protecting and couplinggroups, such as dimethoxytrityl at the 5′-end, and phosphoramidites atthe 3′-end. The average stepwise coupling yields were >98%. Inactiveribozymes were synthesized by substituting a U for G₅ and a U for A₁₄(numbering from (Hertel, K. J., et al., 1992, Nucleic Acids Res., 20,3252)). Hairpin ribozymes are synthesized in two parts and annealed toreconstruct the active ribozyme (Chowrira, B. M. and Burke, J. M., 1992,Nucleic Acids Res., 20, 2835-2840). All ribozymes are modified toenhance stability by modification of five ribonucleotides at both the 5′and 3′ ends with 2′-O-methyl groups. Ribozymes are purified by gelelectrophoresis using general methods or are purified by high pressureliquid chromatography (HPLC; See Usman et al., Synthesis, deprotection,analysis and purification of RNA and ribozymes, filed May, 18, 1994,U.S. Ser. No. 08/245,736 the totality of which is hereby incorporatedherein by reference.) and are resuspended in water.

[0044] The sequences of the chemically synthesized ribozymes useful inthis study are shown in Tables IV-VII. Those in the art will recognizethat these sequences are representative only of many more such sequenceswhere the enzymatic portion of the ribozyme (all but the binding arms)is altered to affect activity and may be formed of ribonucleotides orother nucleotides or non-nucleotides. Such ribozymes are equivalent tothe ribozymes described specifically in the Tables.

[0045] Optimizing Ribozyme Activity

[0046] Ribozyme activity can be optimized as described by Stinchcomb etal., supra. The details will not be repeated here, but include alteringthe length of the ribozyme binding arms (stems I and III, see FIG. 2c),or chemically synthesizing ribozymes with modifications that preventtheir degradation by serum ribonucleases (see e.g., Eckstein et al.,International Publication No. WO 92/07065; Perrault et al., Nature 1990,344:565; Pieken et al., Science 1991, 253:314; Usman and Cedergren,Trends in Biochem. Sci. 1992, 17:334; Usman et al., InternationalPublication No. WO 93/15187; and Rossi et al., International PublicationNo. WO 91/03162, as well as Usman, N. et al. U.S. patent applicationSer. No. 07/829,729, and Sproat, B. European Patent Application92110298.4 which describe various chemical modifications that can bemade to the sugar moieties of enzymatic RNA molecules. All thesepublications are hereby incorporated by reference herein.),modifications which enhance their efficacy in cells, and removal of stemII bases to shorten RNA synthesis times and reduce chemicalrequirements.

[0047] Sullivan, et al., supra, describes the general methods fordelivery of enzymatic RNA molecules. Ribozymes may be administered tocells by a variety of methods known to those familiar to the art,including, but not restricted to, encapsulation in liposomes, byiontophoresis, or by incorporation into other vehicles, such ashydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesivemicrospheres. For some indications, ribozymes may be directly deliveredex vivo to cells or tissues with or without the aforementioned vehicles.Alternatively, the RNA/vehicle combination is locally delivered bydirect injection or by use of a catheter, infusion pump or stent. Otherroutes of delivery include, but are not limited to, intrvascular,intramuscular, subcutaneous or joint injection, aerosol inhalation, oral(tablet or pill form), topical, systemic, ocular, intraperitoneal and/orintrathecal delivery. More detailed descriptions of ribozyme deliveryand administration are provided in Sullivan, et al., supra and Draper,et al., supra which have been incorporated by reference herein.

[0048] Another means of accumulating high concentrations of aribozyme(s) within cells is to incorporate the ribozyme-encodingsequences into a DNA expression vector. Transcription of the ribozymesequences are driven from a promoter for eukaryotic RNA polymerase I(pol I), RNA polymerase II (pol II), or RNA polymerase III (pol III).Transcripts from pol II or pol III promoters will be expressed at highlevels in all cells; the levels of a given pol II promoter in a givencell type will depend on the nature of the gene regulatory sequences(enhancers, silencers, etc.) present nearby. Prokaryotic RNA polymerasepromoters are also used, providing that the prokaryotic RNA polymeraseenzyme is expressed in the appropriate cells (Elroy-Stein, O. and Moss,B., 1990, Proc. Natl. Acad. Sci. USA, 87, 6743-7; Gao, X. and Huang, L.,1993, Nucleic Acids Res., 21, 2867-72; Lieber, A., et al., 1993, MethodsEnzymol., 217, 47-66; Zhou, Y., et al., 1990, Mol. Cell. Biol., 10,4529-37). Several investigators have demonstrated that ribozymesexpressed from such promoters can function in mammalian cells (e.g.(Kashani-Sabet, M., et al., 1992, Antisense Res. Dev., 2, 3-15; Ojwang,J. O., et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 10802-6; Chen, C.J., et al., 1992, Nucleic Acids Res., 20, 4581-9; Yu, M., et al., 1993,Proc. Natl. Acad. Sci. USA, 96, 6340-4; L'Huillier, P. J., et al., 1992,Embo J., 11, 4411-8; Lisziewicz, J., et al., 1993, Proc. Natl. Acad.Sci. U.S.A., 90, 8000-4)). The above ribozyme transcription units can beincorporated into a variety of vectors for introduction into mammaliancells, including but not restricted to, plasmid DNA vectors, viral DNAvectors (such as adenovirus or adeno-associated vectors), or viral RNAvectors (such as retroviral vectors).

[0049] In a preferred embodiment of the invention, a transcription unitexpressing a ribozyme that cleaves relA RNA is inserted into a plasmidDNA vector or an adenovirus DNA viral vector. Both vectors have beenused to transfer genes to the intact vasculature or to joints of liveanimals (Willard, J. E., et al., 1992, Circulation, 86, 1-473.; Nabel,E. G., et al., 1990, Science, 249, 1285-1288.) and both vectors lead totransient gene expression. The adenovirus vector is delivered asrecombinant adenoviral particles. DNA may be delivered alone orcomplexed with vehicles (as described for RNA above). The DNA,DNA/vehicle complexes, or the recombinant adenovirus particles arelocally administered to the site of treatment, e.g., through the use ofan injection catheter, stent or infusion pump or are directly added tocells or tissues ex vivo.

EXAMPLE 1 NF-κB Hammerhead Ribozymes

[0050] By engineering ribozyme motifs we have designed several ribozymesdirected against relA mRNA sequences. These ribozymes are synthesizedwith modifications that improve their nuclease resistance. The abilityof ribozymes to cleave relA target sequences in vitro is evaluated.

[0051] The ribozymes will be tested for function in vivo by analyzingcytokine-induced VCAM-1, ICAM-1, IL-6 and IL-8 expression levels.Ribozymes will be delivered to cells by incorporation into liposomes, bycomplexing with cationic lipids, by microinjection, or by expressionfrom DNA vectors. Cytokine-induced VCAM-1, ICAM-1, IL-6 and IL-8expression will be monitored by ELISA, by indirect immunofluoresence,and/or by FACS analysis. Rel A mRNA levels will be assessed by Northernanalysis, RNAse protection or primer extension analysis or quantitativeRT-PCR. Activity of NF-κB will be monitored by gel-retardation assays.Ribozymes that block the induction of NF-κB activity and/or rel A mRNAby more than 50% will be identified.

[0052] RNA ribozymes and/or genes encoding them will be locallydelivered to transplant tissue ex vivo in animal models. Expression ofthe ribozyme will be monitored by its ability to block ex vivo inductionof VCAM-1, ICAM-1, IL-6 and IL-8 mRNA and protein. The effect of theanti-rel A ribozymes on graft rejection will then be assessed.Similarly, ribozymes will be introduced into joints of mice withcollagen-induced arthritis or rabbits with Streptococcal cellwall-induced arthritis. Liposome delivery, cationic lipid delivery, oradeno-associated virus vector delivery can be used. One dose (or a fewinfrequent doses) of a stable anti-relA ribozyme or a gene constructthat constitutively expresses the ribozyme may abrogate inflammatory andimmune responses in these diseases.

[0053] Uses

[0054] A therapeutic agent that inhibits cytokine gene expression,inhibits adhesion molecule expression, and mimics the anti-inflammatoryeffects of glucocorticoids (without inducing steroid-responsive genes)is ideal for the treatment of inflammatory and autoimmune disorders.Disease targets for such a drug are numerous. Target indications and thedelivery options each entails are summarized below. In all cases,because of the potential immunosuppressive properties of a ribozyme thatcleaves rel A mRNA, uses are limited to local delivery, acuteindications, or ex vivo treatment.

[0055] *Rheumatoid Arthritis (RA).

[0056] Due to the chronic nature of RA, a gene therapy approach islogical. Delivery of a ribozyme to inflamed joints is mediated byadenovirus, retrovirus, or adeno-associated virus vectors. For instance,the appropriate adenovirus vector can be administered by directinjection into the synovium: high efficiency of gene transfer andexpression for several months would be expected (B. J. Roessler, E. D.Allen, J. M. Wilson, J. W. Hartman, B. L. Davidson, J. Clin. Invest. 92,1085-1092 (1993)). It is unlikely that the course of the disease couldbe reversed by the transient, local administration of ananti-inflammatory agent. Multiple administrations may be necessary.Retrovirus and adeno-associated virus vectors would lead to permanentgene transfer and expression in the joint. However, permanent expressionof a potent anti-inflammatory agent may lead to local immune deficiency.

[0057] Restenosis.

[0058] Expression of NF-κB in the vessel wall of pigs causes a narrowingof the luminal space due to excessive deposition of extracellular matrixcomponents. This phenotype is similar to matrix deposition that occurssubsequent to coronary angioplasty. In addition, NF-κB is required forthe expression of the oncogene c-myb (F. A. La Rosa, J. W. Pierce, G. E.Soneneshein, Mol. Cell. Biol. 14, 1039-44 (1994)). Thus NF-κB inducessmooth muscle proliferation and the expression of excess matrixcomponents: both processes are thought to contribute to reocclusion ofvessels after coronary angioplasty.

[0059] *Transplantation.

[0060] NF-κB is required for the induction of adhesion molecules (Eck etal., supra, K. O'Brien, et al., J. Clin. Invest. 92, 945-951 (1993))that function in immune recognition and inflammatory responses. At leasttwo potential modes of treatment are possible. In the first,transplanted organs are treated ex vivo with ribozymes or ribozymeexpression vectors. Transient inhibition of NF-κB in the transplantedendothelium may be sufficient to prevent transplant-associatedvasculitis and may significantly modulate graft rejection. In thesecond, donor B cells are treated ex vivo with ribozymes or ribozymeexpression vectors. Recipients would receive the treatment prior totransplant. Treatment of a recipient with B cells that do not express Tcell co-stimulatory molecules (such as ICAM-1, VCAM-1, and/or B7 anB7-2) can induce antigen-specific anergy. Tolerance to the donor'shistocompatibility antigens could result; potentially, any donor couldbe used for any transplantation procedure.

[0061] *Asthma.

[0062] Granulocyte macrophage colony stimulating factor (GM-CSF) isthought to play a major role in recruitment of eosinophils and otherinflammatory cells during the late phase reaction to asthmatic trauma.Again, blocking the local induction of GM-CSF and other inflammatorymediators is likely to reduce the persistent inflammation observed inchronic asthmatics. Aerosol delivery of ribozymes or adenovirus ribozymeexpression vectors is a feasible treatment.

[0063] Gene Therapy.

[0064] Immune responses limit the efficacy of many gene transfertechniques. Cells transfected with retrovirus vectors have shortlifetimes in immune competent individuals. The length of expression ofadenovirus vectors in terminally differentiated cells is longer inneonatal or immune-compromised animals. Insertion of a small ribozymeexpression cassette that modulates inflammatory and immune responsesinto existing adenovirus or retrovirus constructs will greatly enhancetheir potential.

[0065] Thus, ribozymes of the present invention that cleave rel A mRNAand thereby NF-κB activity have many potential therapeutic uses, andthere are reasonable modes of delivering the ribozymes in a number ofthe possible indications. Development of an effective ribozyme thatinhibits NF-κB function is described above; available cellular andactivity assays are number, reproducible, and accurate. Animal modelsfor NF-κB function (Kitajima, et al., supra) and for each of thesuggested disease targets exist and can be used to optimize activity.

[0066] Diagnostic Uses

[0067] Ribozymes of this invention may be used as diagnostic tools toexamine genetic drift and mutations within diseased cells. The closerelationship between ribozyme activity and the structure of the targetRNA allows the detection of mutations in any region of the moleculewhich alters the base-pairing and three-dimensional structure of thetarget RNA. By using multiple ribozymes described in this invention, onemay map nucleotide changes which are important to RNA structure andfunction in vitro, as well as in cells and tissues. Cleavage of targetRNAs with ribozymes may be used to inhibit gene expression and definethe role (essentially) of specified gene products in the progression ofdisease. In this manner, other genetic targets may be defined asimportant mediators of the disease. These experiments will lead tobetter treatment of the disease progression by affording the possibilityof combinational therapies (e.g., multiple ribozymes targeted todifferent genes, ribozymes coupled with known small molecule inhibitors,or intermittent treatment with combinations of ribozymes and/or otherchemical or biological molecules). Other in vitro uses of ribozymes ofthis invention are well known in the art, and include detection of thepresence of mRNA associated with an NF-κB related condition. Such RNA isdetected by determining the presence of a cleavage product aftertreatment with a ribozyme using standard methodology.

[0068] In a specific example, ribozymes which can cleave only wild-typeor mutant forms of the target RNA are used for the assay. The firstribozyme is used to identify wild-type RNA present in the sample and thesecond ribozyme will be used to identify mutant RNA in the sample. Asreaction controls, synthetic substrates of both wild-type and mutant RNAwill be cleaved by both ribozymes to demonstrate the relative ribozymeefficiencies in the reactions and the absence of cleavage of the“non-targeted” RNA species. The cleavage products from the syntheticsubstrates will also serve to generate size markers for the analysis ofwild-type and mutant RNAs in the sample population. Thus each analysiswill require two ribozymes, two substrates and one unknown sample whichwill be combined into six reactions. The presence of cleavage productswill be determined using an RNAse protection assay so that full-lengthand cleavage fragments of each RNA can be analyzed in one lane of apolyacrylamide gel. It is not absolutely required to quantify theresults to gain insight into the expression of mutant RNAs and putativerisk of the desired phenotypic changes in target cells. The expressionof mRNA whose protein product is implicated in the development of thephenotype (i.e., NF-κB) is adequate to establish risk. If probes ofcomparable specific activity are used for both transcripts, then aqualitative comparison of RNA levels will be adequate and will decreasethe cost of the initial diagnosis. Higher mutant form to wild-typeratios will be correlated with higher risk whether RNA levels arecompared qualitatively or quantitatively.

[0069] Other embodiments are within the following claims. TABLE ICharacteristics of Ribozymes Group I Introns Size: ˜200 to >1000nucleotides. Requires a U in the target sequence immediately 5′ of thecleavage site. Binds 4-6 nucleotides at 5′ side of cleavage site. Over75 known members of this class. Found in Tetrahymena thermophila rRNA,fungal mitochondria, chloroplasts, phage T4, blue-green algae, andothers. RNAseP RNA (M1 RNA) Size: ˜290 to 400 nucleotides. RNA portionof a ribonucleoprotein enzyme. Cleaves tRNA precursors to form maturetRNA. Roughly 10 known members of this group all are bacterial inorigin. Hammerhead Ribozyme Size: ˜13 to 40 nucleotides. Requires thetarget sequence UH immediately 5′ of the cleavage site. Binds a variablenumber nucleotides on both sides of the cleavage site. 14 known membersof this class. Found in a number of plant pathogens (virusoids) that useRNA as the infectious agent (FIGS. 1 and 2 show examples of variousmanifestations as used in the art). Hairpin Ribozyme Size: ˜50nucleotides. Requires the target sequence GUC immediately 3′ of thecleavage site. Binds 4-6 nucleotides at 5′ side of the cleavage site anda variable number to the 3′ side of the cleavage site. Only 3 knownmember of this class. Found in three plant pathogen (satellite RNAs ofthe tobacco ringspot virus, arabis mosaic virus and chicory yellowmottle virus) which uses RNA as the infectious agent (FIG. 3). HepatitisDelta Virus (HDV) Ribozyme Size: 50-60 nucleotides (at present).Cleavage of target RNAs recently demonstrated. Sequence requirements notfully determined. Binding sites and structural requirements not fullydetermined, although no sequences 5′ of cleavage site are required. Only1 known member of this class. Found in human HDV (FIG. 4). Neurospora VSRNA Ribozyme Size: ˜144 nucleotides (at present) Cleavage of target RNAsrecently demonstrated. Sequence requirements not fully determined.Binding sites and structural requirements not fully determined. Only 1known member of this class. Found in Neurospora VS RNA (FIG. 5).

[0070] TABLE II Mouse rel A HH Target sequence nt. HH Target Seq. ID nt.HH Target Seq. Pos. Sequence No. Pos. Sequence ID No. 19 AAUGGCU acaCaGgA 7 467 cCAGGCU c cuguUCg 108 22 aGCUCcU a cGUgGUG 8 469 AaGCcAU uAGcCAGC 109 26 CcUCcaU u GcGgACa 9 473 UuUgAGU C AGauCAg 110 93 GAuCUGUU uCCCCUC 10 481 AGCGaAU C CAGACCA 111 94 AuCUGUU u CCCCUCA 11 501AACCCCU U uCAcGUU 112 100 UuCCCCU C AUCUUuC 12 502 ACCCCUU u CAcGUUC 113103 CCCUCAU C UuuCCcu 13 508 UuCAcGU U CCUAUAG 114 105 CUCAUCU U uCCcuCA14 509 uCAcGUU C CUAUAGA 115 106 UCAUCUU u CccuCAG 15 512 cGUUCCU AUAGAgGA 116 129 CAGGCuU C UGGgCCu 16 514 UUCCUAU A GAgGAGC 117 138GGgCCuU A UGUGGAG 17 534 GGGGACU A uGACuUG 118 148 UGGAGAU C AucGAaC 18556 UGCGcCU C UGCUUCC 119 151 AGAUCAU c GaaCAGC 19 561 CUCUGCU U CCAGGUG120 180 AUGCGaU U CCGCUAu 20 562 UCUGCUU C CAGGUGA 121 181 UGCGaUU CCGCUAuA 21 585 aAgCCAU u AGcCAGc 122 186 UUCCGCU A uAAaUGC 22 598GGCCCCU C CuCCUGa 123 204 GGGCGCU C aGCGGGC 23 613 CcCCUGU C CUcuCaC 124217 GCAGuAU U CcuGGCG 24 616 CUGUCCU c uCaCAUC 125 239 CACAGAU A CCACCAA25 617 gucCCUU C CUCAgCC 126 262 CCACCAU C AAGAUCA 26 620 CCUUCCU CAgCCaug 127 268 UCAAGAU C AAUGGCU 27 623 UCCUgcU u CCAUCUc 128 276AAUGGCU A CACAGGA 28 628 AUCCGAU U UUUGAUA 129 301 UuCGaAU C UCCCUGG 29630 CCgAUuU U UGAuAAc 130 303 CGaAUCU C CCUGGUC 30 631 CgAUuUU U GAuAAcC131 310 CCCUGGU C ACCAAGG 31 638 UGgCcAU u GUGuuCC 132 323 GGcCCCU CCUCcuga 32 661 CCGAGCU C AAGAUCU 133 326 uCCaCCU C ACCGGCC 33 667UCAAGAU C UGCCGAG 134 335 CCGGCCU C AuCCaCA 34 687 CGgAACU C UGGgAGC 135349 AuGAaCU U GugGGgA 35 700 GCUGCCU C GGUGGGG 136 352 AGaUcaU c GaAcAGc36 715 AUGAGAU C UUCuUgC 137 375 GAUGGCU a CUAUGAG 37 717 GAGAUCU UCuUgCUG 138 376 AUGGucU C UccGgaG 38 718 AGAUCUU C uUgCUGU 139 378GGCUaCU A UGAGGCU 39 721 UucUCCU c CauUGcG 140 391 CUGAcCU C UGCCCaG 40751 AaGACAU U GAGGUGU 141 409 GCaGuAU C CauAGcU 41 759 GAGGUGU A UUUCACG142 416 CCgCAGU a UCCAuAg 42 761 GGUGUAU U UCACGGG 143 417 CAuAGcU UCCAGAAC 43 762 GUGUAUU U CACGGGA 144 418 AuAGcUU C CAGAACC 44 763UGUAUUU C ACGGGAC 145 433 UGGGgAU C CAGUGUG 45 792 CGAGGCU C CUUUUCu 146795 GGCUCCU U UUCuCAA 46 1167 GAUGAGU U UuCCcCC 147 796 GCUCCUU UUcuCAAG 47 1168 AUGAGUU U uCCcCCA 148 797 CUCCUUU U CuCAAGC 48 1169UGAGUUU u CCcCCAU 149 798 UCCUUUU C uCAAGCU 49 1182 AUGcUGU U aCCaUCa150 829 UGGCCAU U GUGUUCC 50 1183 UGcUGUU a CCaUCaG 151 834 AUUGUGU UCCGGACu 51 1184 GGccccU C CUcCUGa 152 835 UUGUGUU C CGGACuC 52 1187GUccCuU c CUcAGCc 153 845 GACuCCU C CgUACGC 53 1188 UUaCCaU C aGGGCAG154 849 CCUCCgU A CGCcGAC 54 1198 GGgAGuU u AGuCuGa 155 872 cCAGGCU CCUGUuCG 55 1209 CAGcCCU a caCCUUc 156 883 UuCGaGU C UCCAUGC 56 1215cuGGCCU U aGCaCCG 157 885 CGaGUCU C CAUGCAG 57 1229 GGuCCCU u CCucAGc158 905 GCGGCCU U CuGAuCG 58 1237 CCCAgcU C CUGCCCC 159 906 CGGCCUU CuGAuCGc 59 1250 CCAGcCU C CAGgCUC 160 919 GcGAGCU C AGUGAGC 60 1268CCCaGCU C CuGCCcc 161 936 AUGGAgU U CCAGUAC 61 1279 CCAUGGU c cCuuCcu162 937 UGGAgUU C CAGUACu 62 1281 gUGGgcU C AGCUgcG 163 942 UUCCAGU ACuUGCCA 63 1286 AUgAGuU u UccCCCA 164 953 GCCucAU c CacAuGA 64 1309CuCCUGU u CgAGUCu 165 962 AGAuGAU C GcCACCG 65 1315 cCCCAGU u CUAaCCC166 965 CagUacU u gCCaGAc 66 1318 CAGUuCA A aCCCCgG 167 973 ACCGGAU UGaaGAGA 67 1331 gGGuCCU C CcCAGuC 168 986 GAgACcU u cAAGagu 68 1334CuuUuCU C AaGCUGa 169 996 AGGACcU A UGAGACC 69 1389 ACGCUGU C gGAaGCC170 1005 GAGACCU U CAAGAGu 70 1413 CUGCAGU U UGAUGcU 171 1006 AGACCUU CAAGAGuA 71 1414 UGCAGUU U GAUGcUG 172 1015 AGAGuAU C AUGAAGA 72 1437GGGGCCU U GCUUGGC 173 1028 GAAGAGU C CUUUCAa 73 1441 CCUUGCU U GGCAACA174 1031 GAGUCCU U UCAauGG 74 1467 GgaGUGU U CACAGAC 175 1032 AGUCCUU UCaauGGA 75 1468 gaGUGUU C ACAGACC 176 1033 GUCCUUU C AauGGAC 76 1482CUGGCAU C uGUgGAC 177 1058 CCGGCCU C CaaCcCG 77 1486 CuUCgGU a GggAACU178 1064 UaCACCU u GaucCAa 78 1494 GACAACU C aGAGUUU 179 1072 GgCGuAU UGCUGUGC 79 1500 UCaGAGU U UCAGCAG 180 1082 UGUGCCU a CCCGaAa 80 1501CaGAGUU U CAGCAGC 181 1083 aaGCCUU C CCGaAGu 81 1502 aGAGUUU C AGCAGCU182 1092 CGaAaCU C AaCUUCU 82 1525 gGuGCAU c CCUGUGu 183 1097 CUCAaCU UCUGUCCC 83 1566 AUGGAGU A CCCUGAa 184 1098 UCAaCUU C UGUCCCC 84 1577UGAaGCU A UAACUCG 185 1102 CUUCUGU C CCCAAGC 85 1579 AaGCUAU A ACUCGCC186 1125 CAGCCCU A caCCUUc 86 1583 UAUAACU C GCCUgGU 187 1127 GCCaUAU agCcUUAC 87 1588 CUCuCCU A GaGAggG 188 1131 cAUCCCU c agCacCA 88 1622CCCAGCU C CUGCcCC 189 1132 AcaCCUU c cCagCAU 89 1628 UCCUGCU u CggUaGG190 1133 UCCaUcU c CagCuUC 90 1648 CGGGGCU u CCCAAUG 191 1137 UUUACuU uAgCgCgc 91 1660 cUGaCCU C ugccCAG 192 1140 cCagCAU C CCUcAGC 92 1663cuCUgCU U cCAGGuG 193 1153 GCACCAU C AACUuUG 93 1664 uCUgCUU c CAGGuGA194 1158 AUCAACU u UGAUGAG 94 1665 CUCgcUU u cGGAGgU 195 1680 GAAGACU UCUCCUCC 95 1681 AAGACUU C UCCUCCA 96 1683 GACUUCU C CUCCAUU 97 1686UUCUCCU C CAUUGCG 98 1690 CCUCCAU U GCGGACA 99 1704 AUGGACU U CUCuGCu100 1705 UGGACUU C UCuGCuC 101 1707 GACUUCU C uGCuCUu 102 1721 uuUGAGU CAGAUCAG 103 1726 GUCAGAU C AGCUCCU 104 1731 AUCAGCU C CUAAGGu 105 1734AGCUCCU A AGGuGcU 106 1754 CaGugCU C CCaAGAG 107

[0071] TABLE III Human rel A HH Target Sequences nt. HH Target Seq. IDnt. HH Target Seq. ID Pos. Sequence No. Pos. Sequence No. 19 AAUGGCU CGUCUGUA 196 467 GCAGGCU A UCAGUCA 297 22 GGCUCGU C UGUAGUG 197 469AGGCUAU C AGUCAGC 298 26 CGUCUGU A GUGCACG 198 473 UAUCAGU C AGCGCAU 29993 GAACUGU U CCCCCUC 199 481 AGCGCAU C CAGACCA 300 94 AACUGUU C CCCCUCA200 501 AACCCCU U CCAAGUU 301 100 UCCCCCU C AUCUUCC 201 502 ACCCCUU CCAAGUUC 302 103 CCCUCAU C UUCCCGG 202 508 UCCAAGU U CCUAUAG 303 105CUCAUCU U CCCGGCA 203 509 CCAAGUU C CUAUAGA 304 106 UCAUCUU C CCGGCAG204 512 AGUUCCU A UAGAAGA 305 129 CAGGCCU C UGGCCCC 205 514 UUCCUAU AGAAGAGC 306 138 GGCCCCU A UGUGGAG 206 534 GGGGACU A CGACCUG 307 148UGGAGAU C AUUGAGC 207 556 UGCGGCU C UGCUUCC 308 151 AGAUCAU U GAGCAGC208 561 CUCUGCU U CCAGGUG 309 180 AUGCGCU U CCGCUAC 209 562 UCUGCUU CCAGGUGA 310 181 UGCGCUU C CGCUACA 210 585 GACCCAU C AGGCAGG 311 186UUCCGCU A CAAGUGC 211 598 GGCCCCU C CGCCUGC 312 204 GGGCGCU C CGCGGGC212 613 CGCCUGU C CUUCCUC 313 217 GCAGCAU C CCAGGCG 213 616 CUGUCCU UCCUCAUC 314 239 CACAGAU A CCACCAA 214 617 UGUCCUU C CUCAUCC 315 262CCACCAU C AAGAUCA 215 620 CCUUCCU C AUCCCAU 316 268 UCAAGAU C AAUGGCU216 623 UCCUCAU C CCAUCUU 317 276 AAUGGCU A CACAGGA 217 628 AUCCCAU CUUUGACA 318 301 UGCGCAU C UCCCUGG 218 630 CCCAUCU U UGACAAU 319 303CGCAUCU C CCUGGUC 219 631 CCAUCUU U GACAAUC 320 310 CCCUGGU C ACCAAGG220 638 UGACAAU C GUGCCCC 321 323 GGACCCU C CUCACCG 221 661 CCGAGCU CAAGAUCU 322 326 CCCUCCU C ACCGGCC 222 667 UCAAGAU C UGCCGAG 323 335CCGGCCU C ACCCCCA 223 687 CGAAACU C UGGCAGC 324 349 ACGAGCU U GUAGGAA224 700 GCUGCCU C GGUGGGG 325 352 AGCUUGU A GGAAAGG 225 715 AUGAGAU CUUCCUAC 326 375 GAUGGCU U CUAUGAG 226 717 GAGAUCU U CCUACUG 327 376AUGGCUU C UAUGAGG 227 718 AGAUCUU C CUACUGU 328 378 GGCUUCU A UGAGGCU228 721 UCUUCCU A CUGUGUG 329 391 CUGAGCU C UGCCCGG 229 751 AGGACAU UGAGGUGU 330 409 GCUGCAU C CACAGUU 230 759 GAGGUGU A UUUCACG 331 416CCACAGU U UCCAGAA 231 761 GGUGUAU U UCACGGG 332 417 CACAGUU U CCAGAAC232 762 GUGUAUU U CACGGGA 333 418 ACAGUUU C CAGAACC 233 763 UGUAUUU CACGGGAC 334 433 UGGGAAU C CAGUGUG 234 792 CGAGGCU C CUUUUCG 335 795GGCUCCU U UUCGCAA 235 1167 GAUGAGU U UCCCACC 336 796 GCUCCUU U UCGCAAG236 1168 AUGAGUU U CCCACCA 337 797 CUCCUUU U CGCAAGC 237 1169 UGAGUUU CCCACCAU 338 798 UCCUUUU C GCAAGCU 238 1182 AUGGUGU U UCCUUCU 339 829UGGCCAU U GUGUUCC 239 1183 UGGUGUU U CCUUCUG 340 834 AUUGUGU U CCGGACC240 1184 GGUGUUU C CUUCUGG 341 835 UUGUGUU C CGGACCC 241 1187 GUUUCCU UCUGGGCA 342 845 GACCCCU C CCUACGC 242 1188 UUUCCUU C UGGGCAG 343 849CCUCCCU A CGCAGAC 243 1198 GGCAGAU C AGCCAGG 344 872 GCAGGCU C CUGUGCG244 1209 CAGGCCU C GGCCUUG 345 883 UGCGUGU C UCCAUGC 245 1215 UCGGCCU UGGCCCCG 346 885 CGUGUCU C CAUGCAG 246 1229 GGCCCCU C CCCAAGU 347 905GCGGCCU U CCGACCG 247 1237 CCCAAGU C CUGCCCC 348 906 CGGCCUU C CGACCGG248 1250 CCAGGCU C CAGCCCC 349 919 GGGAGCU C AGUGAGC 249 1268 CCCUGCU CCAGCCAU 350 936 AUGGAAU U CCAGUAC 250 1279 CCAUGGU A UCAGGUC 351 937UGGAAUU C CAGUACC 251 1281 AUGGUAU C AGCUCUG 352 942 UUCCAGU A CCUGCCA252 1286 AUCAGCU C UGGCCCA 353 953 GCCAGAU A CAGACGA 253 1309 CCCCUGU CCCAGUCC 354 962 AGACGAU C GUCACCG 254 1315 UCCCAGU C CUAGCCC 355 965CGAUCGU C ACCGGAU 255 1318 CAGUCCU A GCCCCAG 356 973 ACCGGAU U GAGGAGA256 1331 AGGCCCU C CUCAGGC 357 986 GAAACGU A AAAGGAC 257 1334 CCCUCCU CAGGCUGU 358 996 AGGACAU A UGAGACC 258 1389 ACGCUGU C AGAGGCC 359 1005GAGACCU U CAAGAGC 259 1413 CUGCAGU U UGAUGAU 360 1006 AGACCUU C AAGAGCA260 1414 UGCAGUU U GAUGAUG 361 1015 AGAGCAU C AUGAAGA 261 1437 GGGGCCU UGCUUGGC 362 1028 GAAGAGU C CUUUCAG 262 1441 CCUUGCU U GGCAACA 363 1031GAGUCCU U UCAGCGG 263 1467 GCUGUGU U CACAGAC 364 1032 AGUCCUU U CAGCGGA264 1468 CUGUGUU C ACAGACC 365 1033 GUCCUUU C AGCGGAC 265 1482 CUGGCAU CCGUCGAC 366 1058 CCGGCCU C CACCUCG 266 1486 CAUCCGU C GACAACU 367 1064UCCACCU C GACGCAU 267 1494 GACAACU C CGAGUUU 368 1072 GACGCAU U GCUGUGC268 1500 UCCGAGU U UCAGCAG 369 1082 UGUGCCU U CCCGCAG 269 1501 CCGAGUU UCAGCAGC 370 1083 GUGCCUU C CCGCAGC 270 1502 CGAGUUU C AGCAGCU 371 1092CGCAGCU C AGCUUCU 271 1525 AGGGCAU A CCUGUGG 372 1097 CUCAGCU U CUGUCCC272 1566 AUGGAGU A CCCUGAG 373 1098 UCAGCUU C UGUCCCC 273 1577 UGAGGCU AUAACUCG 374 1102 CUUCUGU C CCCAAGC 274 1579 AGGCUAU A ACUCGCC 375 1125CAGCCCU A UCCCUUU 275 1583 UAUAACU C GCCUAGU 376 1127 GCCCUAU C CCUUUAC276 1588 CUCGCCU A GUGACAG 377 1131 UAUCCCU U UACGUCA 277 1622 CCCAGCU CCUGCUCC 378 1132 AUCCCUU U ACGUCAU 278 1628 UCCUGCU C CACUGGG 379 1133UCCCUUU A CGUCAUC 279 1648 CGGGGCU C CCCAAUG 380 1137 UUUACGU C AUCCCUG280 1660 AUGGCCU C CUUUCAG 381 1140 ACGUCAU C CCUGAGC 281 1663 GCCUCCU UUCAGGAG 382 1153 GCACCAU C AACUAUG 282 1664 CCUCCUU U CAGGAGA 383 1158AUCAACU A UGAUGAG 283 1665 CUCCUUU C AGGAGAU 384 1680 GAAGACU U CUCCUCC284 1681 AAGACUU C UCCUCCA 285 1683 GACUUCU C CUCCAUU 286 1686 UUCUCCU CCAUUGCG 287 1690 CCUCCAU U GCGGACA 288 1704 AUGGACU U CUCAGCC 289 1705UGGACUU C UCAGCCC 290 1707 GACUUCU C AGCCCUG 291 1721 GCUGAGU C AGAUCAG292 1726 GUCAGAU C AGCUCCU 293 1731 AUCAGCU C CUAAGGG 294 1734 AGCUCCU AAGGGGGU 295 1754 CUGCCCU C CCCAGAG 296

[0072] TABLE IV Mouse rel A HH Ribozyme Sequences nt. Seq. HH RibozymeSequence Seq. ID No. 19 UCCUGUG CUGAUGAGGCCGAAAGGCCGAA AGCCAUU 385 22CACCACG CUGAUGAGGCCGAAAGGCCGAA AGGAGCU 386 26 UGUCCGCCUGAUGAGGCCGAAAGGCCGAA AUGGAGG 387 93 GAGGGGA CUGAUGAGGCCGAAAGGCCGAAACAGAUC 388 94 UGAGGGG CUGAUGAGGCCGAAAGGCCGAA AACAGAU 389 100 GAAAGAUCUGAUGAGGCCGAAAGGCCGAA AGGGGAA 390 103 AGGGAAA CUGAUGAGGCCGAAAGGCCGAAAUGAGGG 391 105 UGAGGGA CUGAUGAGGCCGAAAGGCCGAA AGAUGAG 392 106 CUGAGGGCUGAUGAGGCCGAAAGGCCGAA AAGAUGA 393 129 AGGCCCA CUGAUGAGGCCGAAAGGCCGAAAAGCCUG 394 138 CUCCACA CUGAUGAGGCCGAAAGGCCGAA AAGGCCC 395 148 GUUCGAUCUGAUGAGGCCGAAAGGCCGAA AUCUCCA 396 151 GCUGUUC CUGAUGAGGCCGAAAGGCCGAAAUGAUCU 397 180 AUAGCGG CUGAUGAGGCCGAAAGGCCGAA AUCGCAU 398 181 UAUAGCGCUGAUGAGGCCGAAAGGCCGAA AAUCGCA 399 186 GCAUUUA CUGAUGAGGCCGAAAGGCCGAAAGCGGAA 400 204 GCCCGCU CUGAUGAGGCCGAAAGGCCGAA AGCGCCC 401 217 CGCCAGGCUGAUGAGGCCGAAAGGCCGAA AUACUGC 402 239 UUGGUGG CUGAUGAGGCCGAAAGGCCGAAAUCUGUG 403 262 UGAUCUU CUGAUGAGGCCGAAAGGCCGAA AUGGUGG 404 268 AGCCAUUCUGAUGAGGCCGAAAGGCCGAA AUCUUGA 405 276 UCCUGUG CUGAUGAGGCCGAAAGGCCGAAAGCCAUU 406 301 CCAGGGA CUGAUGAGGCCGAAAGGCCGAA AUUCGAA 407 303 GACCAGGCUGAUGAGGCCGAAAGGCCGAA AGAUUCG 408 310 CCUUGGU CUGAUGAGGCCGAAAGGCCGAAACCAGGG 409 323 UCAGGAG CUGAUGAGGCCGAAAGGCCGAA AGGGGCC 410 326 GGCCGGUCUGAUGAGGCCGAAAGGCCGAA AGGUGGA 411 335 UGUGGAU CUGAUGAGGCCGAAAGGCCGAAAGGCCGG 412 349 UCCCCAC CUGAUGAGGCCGAAAGGCCGAA AGUUCAU 413 352 GCUGUUCCUGAUGAGGCCGAAAGGCCGAA AUGAUCU 414 375 CUCAUAG CUGAUGAGGCCGAAAGGCCGAAAGCCAUC 415 376 CUCCGGA CUGAUGAGGCCGAAAGGCCGAA AGACCAU 416 378 AGCCUCACUGAUGAGGCCGAAAGGCCGAA AGUAGCC 417 391 CUGGGCA CUGAUGAGGCCGAAAGGCCGAAAGGUCAG 418 391 CUGGGCA CUGAUGAGGCCGAAAGGCCGAA AGGUCAG 428 409 AGCUAUGCUGAUGAGGCCGAAAGGCCGAA AUACUGC 419 416 CUAUGGA CUGAUGAGGCCGAAAGGCCGAAACUGCGG 420 417 GUUCUGG CUGAUGAGGCCGAAAGGCCGAA AGCUAUG 421 418 GGUUCUGCUGAUGAGGCCGAAAGGCCGAA AAGCUAU 422 433 CACACUG CUGAUGAGGCCGAAAGGCCGAAAUCCCCA 423 467 CGAACAG CUGAUGAGGCCGAAAGGCCGAA AGCCUGG 424 469 GCUGGCUCUGAUGAGGCCGAAAGGCCGAA AUGGCUU 425 473 CUGAUCU CUGAUGAGGCCGAAAGGCCGAAACUCAAA 426 481 UGGUCUG CUGAUGAGGCCGAAAGGCCGAA AUUCGCU 427 501 AACGUGACUGAUGAGGCCGAAAGGCCGAA AGGGGUU 428 502 GAACGUG CUGAUGAGGCCGAAAGGCCGAAAAGGGGU 429 508 CUAUAGG CUGAUGAGGCCGAAAGGCCGAA ACGUGAA 430 509 UCUAUAGCUGAUGAGGCCGAAAGGCCGAA AACGUGA 431 512 UCCUCUA CUGAUGAGGCCGAAAGGCCGAAAGGAACG 432 514 GCUCCUC CUGAUGAGGCCGAAAGGCCGAA AUAGGAA 433 534 CAAGUCACUGAUGAGGCCGAAAGGCCGAA AGUCCCC 434 556 GGAAGCA CUGAUGAGGCCGAAAGGCCGAAAGGCGCA 435 561 CACCUGG CUGAUGAGGCCGAAAGGCCGAA AGGAGAG 436 562 UCACCUGCUGAUGAGGCCGAAAGGCCGAA AAGCAGA 437 585 GCUGGCU CUGAUGAGGCCGAAAGGCCGAAAUGGCUU 438 598 UCAGGAG CUGAUGAGGCCGAAAGGCCGAA AGGGGCC 439 613 GUGAGAGCUGAUGAGGCCGAAAGGCCGAA ACAGGGG 440 616 GAUGUGA CUGAUGAGGCCGAAAGGCCGAAAGGACAG 441 617 GGCUGAG CUGAUGAGGCCGAAAGGCCGAA AAGGGAC 442 620 CAUGGCUCUGAUGAGGCCGAAAGGCCGAA AGGAAGG 443 623 GAGAUGG CUGAUGAGGCCGAAAGGCCGAAAGCAGGA 444 628 UAUCAAA CUGAUGAGGCCGAAAGGCCGAA AUCGGAU 445 630 GUUAUCACUGAUGAGGCCGAAAGGCCGAA AAAUCGG 446 631 GGUUAUC CUGAUGAGGCCGAAAGGCCGAAAAAAUCG 447 638 GGAACAC CUGAUGAGGCCGAAAGGCCGAA AUGGCCA 448 661 AGAUCUUCUGAUGAGGCCGAAAGGCCGAA AGCUCGG 449 667 CUCGGCA CUGAUGAGGCCGAAAGGCCGAAAUCUUGA 450 687 GCUCCCA CUGAUGAGGCCGAAAGGCCGAA AGUUCCG 451 700 CCCCACCCUGAUGAGGCCGAAAGGCCGAA AGGCAGC 452 715 GCAAGAA CUGAUGAGGCCGAAAGGCCGAAAUCUCAU 453 717 CAGCAAG CUGAUGAGGCCGAAAGGCCGAA AGAUCUC 454 718 ACAGCAACUGAUGAGGCCGAAAGGCCGAA AAGAUCU 455 721 CGCAAUG CUGAUGAGGCCGAAAGGCCGAAAGGAGAA 456 751 ACACCUC CUGAUGAGGCCGAAAGGCCGAA AUGUCUU 457 759 CGUGAAACUGAUGAGGCCGAAAGGCCGAA ACACCUC 458 761 CCCGUGA CUGAUGAGGCCGAAAGGCCGAAAUACACC 459 762 UCCCGUG CUGAUGAGGCCGAAAGGCCGAA AAUACAC 460 763 GUCCCGUCUGAUGAGGCCGAAAGGCCGAA AAAUACA 461 792 AGAAAAG CUGAUGAGGCCGAAAGGCCGAAAGCCUCG 462 795 UUGAGAA CUGAUGAGGCCGAAAGGCCGAA AGGAGCC 463 796 CUUGAGACUGAUGAGGCCGAAAGGCCGAA AAGGAGC 464 797 GCUUGAG CUGAUGAGGCCGAAAGGCCGAAAAAGGAG 465 798 AGCUUGA CUGAUGAGGCCGAAAGGCCGAA AAAAGGA 466 829 GGAACACCUGAUGAGGCCGAAAGGCCGAA AUGGCCA 467 834 AGUCCGG CUGAUGAGGCCGAAAGGCCGAAACACAAU 468 835 GAGUCCG CUGAUGAGGCCGAAAGGCCGAA AACACAA 469 845 GCGUACGCUGAUGAGGCCGAAAGGCCGAA AGGAGUC 470 849 GUCGGCG CUGAUGAGGCCGAAAGGCCGAAACGGAGG 471 872 CGAACAG CUGAUGAGGCCGAAAGGCCGAA AGCCUGG 472 883 GCAUGGACUGAUGAGGCCGAAAGGCCGAA ACUCGAA 473 885 CUGCAUG CUGAUGAGGCCGAAAGGCCGAAAGACUCG 474 905 CGAUCAG CUGAUGAGGCCGAAAGGCCGAA AGGCCGC 475 906 GCGAUCACUGAUGAGGCCGAAAGGCCGAA AAGGCCG 476 919 GCUCACU CUGAUGAGGCCGAAAGGCCGAAAGCUCGC 477 936 GUACUGG CUGAUGAGGCCGAAAGGCCGAA ACUCCAU 478 937 AGUACUGCUGAUGAGGCCGAAAGGCCGAA AACUCCA 479 942 UGGCAAG CUGAUGAGGCCGAAAGGCCGAAACUGGAA 480 953 UCAUGUG CUGAUGAGGCCGAAAGGCCGAA AUGAGGC 481 962 CGGUGGCCUGAUGAGGCCGAAAGGCCGAA AUCAUCU 482 965 GUCUGGC CUGAUGAGGCCGAAAGGCCGAAAGUACUG 483 973 UCUCUUC CUGAUGAGGCCGAAAGGCCGAA AUCCGGU 484 986 ACUCUUGCUGAUGAGGCCGAAAGGCCGAA AGGUCUC 485 1005 ACUCUUG CUGAUGAGGCCGAAAGGCCGAAAGGUCUC 486 1006 UACUCUU CUGAUGAGGCCGAAAGGCCGAA AAGGUCU 487 1015 UCUUCAUCUGAUGAGGCCGAAAGGCCGAA AUACUCU 488 1028 UUGAAAG CUGAUGAGGCCGAAAGGCCGAAACUCUUC 490 1031 CCAUUGA CUGAUGAGGCCGAAAGGCCGAA AGGACUC 491 1032 UCCAUGGCUGAUGAGGCCGAAAGGCCGAA AAGGACU 492 1033 GUCCAUU CUGAUGAGGCCGAAAGGCCGAAAAAGGAC 493 1058 CGGGUUG CUGAUGAGGCCGAAAGGCCGAA AGGCCGG 494 1064 UUGGAUCCUGAUGAGGCCGAAAGGCCGAA AGGUGUA 495 1072 GCACAGC CUGAUGAGGCCGAAAGGCCGAAAUACGCC 496 1082 UUUCGGG CUGAUGAGGCCGAAAGGCCGAA AGGCACA 497 1083 ACUUCGGCUGAUGAGGCCGAAAGGCCGAA AAGGCUU 498 1092 AGAAGUU CUGAUGAGGCCGAAAGGCCGAAAGUUUCG 499 1097 GGGACAG CUGAUGAGGCCGAAAGGCCGAA AGUUGAG 500 1098 GGGGACACUGAUGAGGCCGAAAGGCCGAA AAGUUGA 501 1102 GCUUGGG CUGAUGAGGCCGAAAGGCCGAAACAGAAG 502 1125 GAAGGUG CUGAUGAGGCCGAAAGGCCGAA AGGGCUG 503 1127 GUAAGGCCUGAUGAGGCCGAAAGGCCGAA AUAUGGC 504 1131 UGGUGCU CUGAUGAGGCCGAAAGGCCGAAAGGGAUG 505 1132 AUGCUGG CUGAUGAGGCCGAAAGGCCGAA AAGGUGU 506 1133 GAAGCUGCUGAUGAGGCCGAAAGGCCGAA AGAUGGA 507 1137 GCGCGCU CUGAUGAGGCCGAAAGGCCGAAAAGUAAA 508 1140 GCUGAGG CUGAUGAGGCCGAAAGGCCGAA AUGCUGG 509 1153 CAAAGUUCUGAUGAGGCCGAAAGGCCGAA AUGGUGC 510 1158 CUCAUCA CUGAUGAGGCCGAAAGGCCGAAAGUUGAU 511 1167 GGGGGAA CUGAUGAGGCCGAAAGGCCGAA ACUCAUC 512 1168 UGGGGGACUGAUGAGGCCGAAAGGCCGAA AACUCAU 513 1169 AUGGGGG CUGAUGAGGCCGAAAGGCCGAAAAACUCA 514 1182 UGAUGGU CUGAUGAGGCCGAAAGGCCGAA ACAGCAU 515 1183 CUGAUGGCUGAUGAGGCCGAAAGGCCGAA AACAGCA 516 1184 UCAGGAG CUGAUGAGGCCGAAAGGCCGAAAGGGGCC 517 1187 GGCUGAG CUGAUGAGGCCGAAAGGCCGAA AAGGGAC 518 1188 CUGCCCUCUGAUGAGGCCGAAAGGCCGAA AUGGUAA 519 1198 UCAGACU CUGAUGAGGCCGAAAGGCCGAAAACUCCC 520 1209 GAAGGUG CUGAUGAGGCCGAAAGGCCGAA AGGGCUG 521 1215 CGGUGCUCUGAUGAGGCCGAAAGGCCGAA AGGCCAG 522 1229 GCUGAGG CUGAUGAGGCCGAAAGGCCGAAAGGGACC 523 1237 GGGGCAG CUGAUGAGGCCGAAAGGCCGAA AGCUGGG 524 1250 GAGCCUGCUGAUGAGGCCGAAAGGCCGAA AGGCUGG 525 1268 GGGGCAG CUGAUGAGGCCGAAAGGCCGAAAGCUGGG 526 1279 AGGAAGG CUGAUGAGGCCGAAAGGCCGAA ACCAUGG 527 1281 CGCAGCUCUGAUGAGGCCGAAAGGCCGAA AGCCCAC 528 1286 UGGGGGA CUGAUGAGGCCGAAAGGCCGAAAACUCAU 529 1309 AGACUCG CUGAUGAGGCCGAAAGGCCGAA ACAGGAG 530 1315 GGGUUAGCUGAUGAGGCCGAAAGGCCGAA ACUGGGG 531 1318 CCGGGGU CUGAUGAGGCCGAAAGGCCGAAAGAACUG 532 1331 GACUGGG CUGAUGAGGCCGAAAGGCCGAA AGGACCC 533 1334 UCAGCUUCUGAUGAGGCCGAAAGGCCGAA AGAAAAG 534 1389 GGCUUCC CUGAUGAGGCCGAAAGGCCGAAACAGCGU 535 1413 AGCAUCA CUGAUGAGGCCGAAAGGCCGAA ACUGGAG 536 1414 CAGCAUCCUGAUGAGGCCGAAAGGCCGAA AACUGCA 537 1437 GCCAAGC CUGAUGAGGCCGAAAGGCCGAAAGGCCCC 538 1441 UGUUGCC CUGAUGAGGCCGAAAGGCCGAA AGCAAGG 539 1467 GUCUGUGCUGAUGAGGCCGAAAGGCCGAA ACACUCC 540 1468 GGUCUGU CUGAUGAGGCCGAAAGGCCGAAAACACUC 541 1482 GUCCACA CUGAUGAGGCCGAAAGGCCGAA AUGCCAG 542 1486 AGUUCCCCUGAUGAGGCCGAAAGGCCGAA ACCGAAG 543 1494 AAACUCU CUGAUGAGGCCGAAAGGCCGAAAGUUGUC 544 1500 CUGCUGA CUGAUGAGGCCGAAAGGCCGAA ACUCUGA 545 1501 GCUGCUGCUGAUGAGGCCGAAAGGCCGAA AACUCUG 546 1502 AGCUGCU CUGAUGAGGCCGAAAGGCCGAAAAACUCU 547 1525 ACACAGG CUGAUGAGGCCGAAAGGCCGAA AUGCACC 548 1566 UUCAGGGCUGAUGAGGCCGAAAGGCCGAA ACUCCAU 549 1577 CGAGUUA CUGAUGAGGCCGAAAGGCCGAAAGCUUCA 550 1579 GGCGAGU CUGAUGAGGCCGAAAGGCCGAA AUAGCUU 551 1583 ACCAGGCCUGAUGAGGCCGAAAGGCCGAA AGUUAUA 552 1588 CCCUCUC CUGAUGAGGCCGAAAGGCCGAAAGGAGAG 553 1622 GGGGCAG CUGAUGAGGCCGAAAGGCCGAA AGCUGGG 554 1628 CCUACCGCUGAUGAGGCCGAAAGGCCGAA AGCAGGA 555 1648 CAUUGGG CUGAUGAGGCCGAAAGGCCGAAAGCCCCG 556 1660 CUGGGCA CUGAUGAGGCCGAAAGGCCGAA AGGUCAG 557 1663 CACCUGGCUGAUGAGGCCGAAAGGCCGAA AGCAGAG 558 1664 UCACCUG CUGAUGAGGCCGAAAGGCCGAAAAGCAGA 559 1665 ACCUCCG CUGAUGAGGCCGAAAGGCCGAA AAGCGAG 560 1680 GGAGGAGCUGAUGAGGCCGAAAGGCCGAA AGUCUUC 561 1681 UGGAGGA CUGAUGAGGCCGAAAGGCCGAAAAGUCUU 562 1683 AAUGGAG CUGAUGAGGCCGAAAGGCCGAA AGAAGUC 563 1686 CGCAAUGCUGAUGAGGCCGAAAGGCCGAA AGGAGAA 564 1690 UGUCCGC CUGAUGAGGCCGAAAGGCCGAAAUGGAGG 565 1704 AGCAGAG CUGAUGAGGCCGAAAGGCCGAA AGUCCAU 566 1705 GAGCAGACUGAUGAGGCCGAAAGGCCGAA AAGUCCA 567 1707 AAGAGCA CUGAUGAGGCCGAAAGGCCGAAAGAAGUC 568 1721 CUGAUCU CUGAUGAGGCCGAAAGGCCGAA ACUCAAA 569 1726 AGGAGCUCUGAUGAGGCCGAAAGGCCGAA AUCUGAC 570 1731 ACCUUAG CUGAUGAGGCCGAAAGGCCGAAAGCUGAU 571 1734 AGCACCU CUGAUGAGGCCGAAAGGCCGAA AGGAGCU 572 1754 CUCUUGGCUGAUGAGGCCGAAAGGCCGAA AGCACUG 573

[0073] TABLE V Human rel A HH Ribozyme Sequences nt. Sequence HHRibozyme Sequence SEQ ID NO. 19 UACAGAC CUGAUGAGGCCGAAAGGCCGAA AGCCAUU574 22 CACUACA CUGAUGAGGCCGAAAGGCCGAA ACGAGCC 575 26 CGUGCACCUGAUGAGGCCGAAAGGCCGAA ACAGACG 576 93 GAGGGGG CUGAUGAGGCCGAAAGGCCGAAACAGUUC 577 94 UGAGGGG CUGAUGAGGCCGAAAGGCCGAA AACAGUU 578 100 GGAAGAUCUGAUGAGGCCGAAAGGCCGAA AGGGGGA 579 103 CCGGGAA CUGAUGAGGCCGAAAGGCCGAAAUGAGGG 580 105 UGCCGGG CUGAUGAGGCCGAAAGGCCGAA AGAUGAG 581 106 CUGCCGGCUGAUGAGGCCGAAAGGCCGAA AAGAUGA 582 129 GGGGCCA CUGAUGAGGCCGAAAGGCCGAAAGGCCUG 583 138 CUCCACA CUGAUGAGGCCGAAAGGCCGAA AGGGGCC 584 148 GCUCAAUCUGAUGAGGCCGAAAGGCCGAA AUCUCCA 585 151 GCUGCUC CUGAUGAGGCCGAAAGGCCGAAAUGAUCU 586 180 GUAGCGG CUGAUGAGGCCGAAAGGCCGAA AGCGCAU 587 181 UGUAGCGCUGAUGAGGCCGAAAGGCCGAA AAGCGCA 588 186 GCACUUG CUGAUGAGGCCGAAAGGCCGAAAGCGGAA 589 204 GCCCGCG CUGAUGAGGCCGAAAGGCCGAA AGCGCCC 590 217 CGCCUGGCUGAUGAGGCCGAAAGGCCGAA AUGCUGC 591 239 UUGGUGG CUGAUGAGGCCGAAAGGCCGAAAUCUGUG 592 262 UGAUCUU CUGAUGAGGCCGAAAGGCCGAA AUGGUGG 593 268 AGCCAUUCUGAUGAGGCCGAAAGGCCGAA AUCUUGA 594 276 UCCUGUG CUGAUGAGGCCGAAAGGCCGAAAGCCAUU 595 301 CCAGGGA CUGAUGAGGCCGAAAGGCCGAA AUGCGCA 596 303 GACCAGGCUGAUGAGGCCGAAAGGCCGAA AGAUGCG 597 310 CCUUGGU CUGAUGAGGCCGAAAGGCCGAAACCAGGG 598 323 CGGUGAG CUGAUGAGGCCGAAAGGCCGAA AGGGUCC 599 326 GGCCGGUCUGAUGAGGCCGAAAGGCCGAA AGGAGGG 600 335 UGGGGGU CUGAUGAGGCCGAAAGGCCGAAAGGCCGG 601 349 UUCCUAC CUGAUGAGGCCGAAAGGCCGAA AGCUCGU 602 352 CCUUUCCCUGAUGAGGCCGAAAGGCCGAA ACAAGCU 603 375 CUCAUAG CUGAUGAGGCCGAAAGGCCGAAAGCCAUC 604 376 CCUCAUA CUGAUGAGGCCGAAAGGCCGAA AAGCCAU 605 378 AGCCUCACUGAUGAGGCCGAAAGGCCGAA AGAAGCC 606 391 CCGGGCA CUGAUGAGGCCGAAAGGCCGAAAGCUCAG 607 409 AACUGUG CUGAUGAGGCCGAAAGGCCGAA AUGCAGC 608 416 UUCUGGACUGAUGAGGCCGAAAGGCCGAA ACUGUGG 609 417 GUUCUGG CUGAUGAGGCCGAAAGGCCGAAAACUGUG 610 418 GGUUCUG CUGAUGAGGCCGAAAGGCCGAA AAACUGU 611 433 CACACUGCUGAUGAGGCCGAAAGGCCGAA AUUCCCA 612 467 UGACUGA CUGAUGAGGCCGAAAGGCCGAAAGCCUGC 613 469 GCUGACU CUGAUGAGGCCGAAAGGCCGAA AUAGCCU 614 473 AUGCGCUCUGAUGAGGCCGAAAGGCCGAA ACUGAUA 615 481 UGGUCUG CUGAUGAGGCCGAAAGGCCGAAAUGCGCU 616 501 AACUUGG CUGAUGAGGCCGAAAGGCCGAA AGGGGUU 617 502 GAACUUGCUGAUGAGGCCGAAAGGCCGAA AAGGGGU 618 508 CUAUAGG CUGAUGAGGCCGAAAGGCCGAAACUUGAA 619 509 UCUAUAG CUGAUGAGGCCGAAAGGCCGAA AACUUGG 620 512 UCUUCUACUGAUGAGGCCGAAAGGCCGAA AGGAACU 621 514 GCUCUUC CUGAUGAGGCCGAAAGGCCGAAAUAGGAA 622 534 CAGGUCG CUGAUGAGGCCGAAAGGCCGAA AGUCCCC 623 556 GGAAGCACUGAUGAGGCCGAAAGGCCGAA AGCCGCA 624 561 CACCUGG CUGAUGAGGCCGAAAGGCCGAAAGCAGAG 625 562 UCACCUG CUGAUGAGGCCGAAAGGCCGAA AAGCAGA 626 585 CCUGCCUCUGAUGAGGCCGAAAGGCCGAA AUGGGUC 627 598 GCAGGCG CUGAUGAGGCCGAAAGGCCGAAAGGGGCC 628 613 GAGGAAG CUGAUGAGGCCGAAAGGCCGAA ACAGGCG 629 616 GAUGAGGCUGAUGAGGCCGAAAGGCCGAA AGGACAG 630 617 GGAUGAG CUGAUGAGGCCGAAAGGCCGAAAAGGACA 631 620 AUGGGAU CUGAUGAGGCCGAAAGGCCGAA AGGAAGG 632 623 AAGAUGGCUGAUGAGGCCGAAAGGCCGAA AUGAGGA 633 628 UGUCAAA CUGAUGAGGCCGAAAGGCCGAAAUCGGAU 634 630 AUUGUCA CUGAUGAGGCCGAAAGGCCGAA AGAUGGG 635 631 GAUUGUCCUGAUGAGGCCGAAAGGCCGAA AAGAUGG 636 638 GGGGCAC CUGAUGAGGCCGAAAGGCCGAAAUUGUCA 637 661 AGAUCUU CUGAUGAGGCCGAAAGGCCGAA AGCUCGG 638 667 CUCGGCACUGAUGAGGCCGAAAGGCCGAA AUCUUGA 639 687 GCUGCCA CUGAUGAGGCCGAAAGGCCGAAAGUUUCG 640 700 CCCCACC CUGAUGAGGCCGAAAGGCCGAA AGGCAGC 641 715 GUAGGAACUGAUGAGGCCGAAAGGCCGAA AUCUCAU 642 717 CAGUAAG CUGAUGAGGCCGAAAGGCCGAAAGAUCUC 643 718 ACAGUAG CUGAUGAGGCCGAAAGGCCGAA AAGAUCU 644 721 CACACAGCUGAUGAGGCCGAAAGGCCGAA AGGAAGA 645 751 ACACCUC CUGAUGAGGCCGAAAGGCCGAAAUGUCCU 646 759 CGUGAAA CUGAUGAGGCCGAAAGGCCGAA ACACCUC 647 761 CCCGUGACUGAUGAGGCCGAAAGGCCGAA AUACACC 648 762 UCCCGUG CUGAUGAGGCCGAAAGGCCGAAAAUACAC 649 763 GUCCCGU CUGAUGAGGCCGAAAGGCCGAA AAAUACA 650 792 CGAAAAGCUGAUGAGGCCGAAAGGCCGAA AGCCUCG 651 795 UUGCGAA CUGAUGAGGCCGAAAGGCCGAAAGGAGCC 652 796 CUUGCGA CUGAUGAGGCCGAAAGGCCGAA AAGGAGC 653 797 GCUUGCGCUGAUGAGGCCGAAAGGCCGAA AAAGGAG 654 798 AGCUUGC CUGAUGAGGCCGAAAGGCCGAAAAAAGGA 655 829 GGAACAC CUGAUGAGGCCGAAAGGCCGAA AUGGCCA 656 834 GGUCCGGCUGAUGAGGCCGAAAGGCCGAA ACACAAU 657 835 GGGUCCG CUGAUGAGGCCGAAAGGCCGAAAACACAA 658 845 GCGUAGG CUGAUGAGGCCGAAAGGCCGAA AGGGGUC 659 849 GUCUGCGCUGAUGAGGCCGAAAGGCCGAA AGGGAGG 660 872 CGCACAG CUGAUGAGGCCGAAAGGCCGAAAGCCUGC 661 883 GCAUGGA CUGAUGAGGCCGAAAGGCCGAA ACACGCA 662 885 CUGCAUGCUGAUGAGGCCGAAAGGCCGAA AGACACG 662 905 CGGUCGG CUGAUGAGGCCGAAAGGCCGAAAGGCCGC 664 906 CCGGUCG CUGAUGAGGCCGAAAGGCCGAA AAGGCCG 665 919 GCUCAGUCUGAUGAGGCCGAAAGGCCGAA AGCUCCC 666 936 GUACUGG CUGAUGAGGCCGAAAGGCCGAAAUUCCAU 667 937 GGUACUG CUGAUGAGGCCGAAAGGCCGAA AAUUCCA 668 942 UGGCAGGCUGAUGAGGCCGAAAGGCCGAA ACUGGAA 669 953 UCGUCUG CUGAUGAGGCCGAAAGGCCGAAAUCUGGC 670 962 CGGUGAC CUGAUGAGGCCGAAAGGCCGAA AUCGUCU 671 965 AUCCGGUCUGAUGAGGCCGAAAGGCCGAA ACGAUCG 672 973 UCUCCUC CUGAUGAGGCCGAAAGGCCGAAAUCCGGU 673 986 GUCCUUU CUGAUGAGGCCGAAAGGCCGAA AGGUUUC 674 996 GGUCUCACUGAUGAGGCCGAAAGGCCGAA AUGUCCU 675 1005 GCUCUUG CUGAUGAGGCCGAAAGGCCGAAAGGUCUC 676 1006 UGCUCUU CUGAUGAGGCCGAAAGGCCGAA AAGGUCU 677 1015 UCUUCAUCUGAUGAGGCCGAAAGGCCGAA AUGCUCU 678 1028 CUGAAAG CUGAUGAGGCCGAAAGGCCGAAACUCUUC 679 1031 CCGCUGA CUGAUGAGGCCGAAAGGCCGAA AGGACUC 680 1032 UCCGCUGCUGAUGAGGCCGAAAGGCCGAA AAGGACU 681 1033 GUCCGCU CUGAUGAGGCCGAAAGGCCGAAAAAGGAC 682 1058 CGAGGUG CUGAUGAGGCCGAAAGGCCGAA AGGCCGG 683 1064 AUGCGUCCUGAUGAGGCCGAAAGGCCGAA AGGUGGA 684 1072 GCACAGC CUGAUGAGGCCGAAAGGCCGAAAUGCGUC 685 1082 CUGCGGG CUGAUGAGGCCGAAAGGCCGAA AGGCACA 686 1083 GCUGCGGCUGAUGAGGCCGAAAGGCCGAA AAGGCAC 687 1092 AGAAGCU CUGAUGAGGCCGAAAGGCCGAAAGCUGCG 688 1097 GGGACAG CUGAUGAGGCCGAAAGGCCGAA AGCUGAG 689 1098 GGGGACACUGAUGAGGCCGAAAGGCCGAA AAGCUGA 690 1102 GCUUGGG CUGAUGAGGCCGAAAGGCCGAAACAGAAG 691 1125 AAAGGGA CUGAUGAGGCCGAAAGGCCGAA AGGGCUG 692 1127 GUAAAGGCUGAUGAGGCCGAAAGGCCGAA AUAGGGC 693 1131 UGACGUA CUGAUGAGGCCGAAAGGCCGAAAGGGAUA 694 1132 AUGACGU CUGAUGAGGCCGAAAGGCCGAA AAGGGAU 695 1133 GAUGACGCUGAUGAGGCCGAAAGGCCGAA AAAGGGA 696 1137 CAGGGAU CUGAUGAGGCCGAAAGGCCGAAACGUAAA 697 1140 GCUCAGG CUGAUGAGGCCGAAAGGCCGAA AUGACGU 698 1153 CAUAGUUCUGAUGAGGCCGAAAGGCCGAA AUGGUGC 699 1158 CUCAUCA CUGAUGAGGCCGAAAGGCCGAAAGUUGAU 700 1167 GGUGGGA CUGAUGAGGCCGAAAGGCCGAA ACUCAUC 701 1168 UGGUGGGCUGAUGAGGCCGAAAGGCCGAA AACUCAU 702 1169 AUGGUGG CUGAUGAGGCCGAAAGGCCGAAAAACUCA 703 1182 AGAAGGA CUGAUGAGGCCGAAAGGCCGAA ACACCAU 704 1183 CAGAAGGCUGAUGAGGCCGAAAGGCCGAA AACACCA 705 1184 CCAGAAG CUGAUGAGGCCGAAAGGCCGAAAAACACC 706 1187 UGCCCAG CUGAUGAGGCCGAAAGGCCGAA AAGAAAC 707 1188 CUGCCCACUGAUGAGGCCGAAAGGCCGAA AAGGAAA 708 1198 CCUGGCU CUGAUGAGGCCGAAAGGCCGAAAUCUGCC 709 1209 GAAGGCC CUGAUGAGGCCGAAAGGCCGAA AGGCCUG 710 1215 CGGGGCCCUGAUGAGGCCGAAAGGCCGAA AGGCCGA 711 1229 ACUUGGG CUGAUGAGGCCGAAAGGCCGAAAGGGGCC 712 1237 GGGGCAG CUGAUGAGGCCGAAAGGCCGAA ACUUGGG 713 1250 GGGGCUGCUGAUGAGGCCGAAAGGCCGAA AGCCUGG 714 1268 AUGGCUG CUGAUGAGGCCGAAAGGCCGAAAGCAGGG 715 1279 GAGCUGA CUGAUGAGGCCGAAAGGCCGAA ACCAUGG 716 1281 CAGAGCUCUGAUGAGGCCGAAAGGCCGAA AUACCAU 717 1286 UGGGCCA CUGAUGAGGCCGAAAGGCCGAAAGCUGAU 718 1309 GGACUGG CUGAUGAGGCCGAAAGGCCGAA ACAGGGG 719 1315 GGGCUAGCUGAUGAGGCCGAAAGGCCGAA ACUGGGA 720 1318 CUGGGGC CUGAUGAGGCCGAAAGGCCGAAAGGACUG 721 1331 GCCUGAG CUGAUGAGGCCGAAAGGCCGAA AGGGCCU 722 1334 ACAGCCUCUGAUGAGGCCGAAAGGCCGAA AGGAGGG 723 1389 GGCCUCU CUGAUGAGGCCGAAAGGCCGAAACAGCGU 724 1413 AUCAUCA CUGAUGAGGCCGAAAGGCCGAA ACUGCAG 725 1414 CAUCAUCCUGAUGAGGCCGAAAGGCCGAA AACUGCA 726 1437 GCCAAGC CUGAUGAGGCCGAAAGGCCGAAAGGCCCC 727 1441 UGUUGCC CUGAUGAGGCCGAAAGGCCGAA AGCAAGG 728 1467 GUCUGUGCUGAUGAGGCCGAAAGGCCGAA ACACAGC 729 1468 GGUCUGU CUGAUGAGGCCGAAAGGCCGAAAACACAG 730 1482 GUCGACG CUGAUGAGGCCGAAAGGCCGAA AUGCCAG 731 1486 AGUUGUCCUGAUGAGGCCGAAAGGCCGAA ACGGAUG 732 1494 AAACUCG CUGAUGAGGCCGAAAGGCCGAAAGUUGUC 733 1500 CUGCUGA CUGAUGAGGCCGAAAGGCCGAA ACUCGGA 734 1501 GCUGCUGCUGAUGAGGCCGAAAGGCCGAA AACUCGG 735 1502 AGCUGCU CUGAUGAGGCCGAAAGGCCGAAAAACUCG 736 1525 CCACAGG CUGAUGAGGCCGAAAGGCCGAA AUGCCCU 737 1566 CACAGGGCUGAUGAGGCCGAAAGGCCGAA ACUCCAU 738 1577 CGAGUUA CUGAUGAGGCCGAAAGGCCGAAAGCCUCA 739 1579 GGCGAGU CUGAUGAGGCCGAAAGGCCGAA AUAGCCU 740 1583 ACCAGGCCUGAUGAGGCCGAAAGGCCGAA AGUUAUA 741 1588 CUGUCAC CUGAUGAGGCCGAAAGGCCGAAAGGCGAG 742 1622 GGAGCAG CUGAUGAGGCCGAAAGGCCGAA AGCUGGG 743 1628 CCCAGUGCUGAUGAGGCCGAAAGGCCGAA AGCAGGA 744 1648 CAUUGGG CUGAUGAGGCCGAAAGGCCGAAAGCCCCG 745 1660 CUGAAAG CUGAUGAGGCCGAAAGGCCGAA AGGCCAU 746 1663 CUCCUGACUGAUGAGGCCGAAAGGCCGAA AGGAGGC 747 1664 UCUCCUG CUGAUGAGGCCGAAAGGCCGAAAAGGAGG 748 1665 AUCUCCU CUGAUGAGGCCGAAAGGCCGAA AAAGGAG 749 1680 GGAGGAGCUGAUGAGGCCGAAAGGCCGAA AGUCUUC 750 1681 UGGAGGA CUGAUGAGGCCGAAAGGCCGAAAAGUGUU 751 1683 AAUGGAG CUGAUGAGGCCGAAAGGCCGAA AGAAGUC 752 1686 CGCAAUGCUGAUGAGGCCGAAAGGCCGAA AGGAGAA 753 1690 UGUCCGC CUGAUGAGGCCGAAAGGCCGAAAUGGAGG 754 1704 GGCUGAG CUGAUGAGGCCGAAAGGCCGAA AGUCCAU 755 1705 GGGCUGACUGAUGAGGCCGAAAGGCCGAA AAGUCCA 756 1707 CAGGGCU CUGAUGAGGCCGAAAGGCCGAAAGAAGUC 757 1721 CUGAUCU CUGAUGAGGCCGAAAGGCCGAA ACUCAGC 758 1726 AGGAGCUCUGAUGAGGCCGAAAGGCCGAA AUCUGAC 759 1731 CCCUUAG CUGAUGAGGCCGAAAGGCCGAAAGCUGAU 760 1734 ACCCCCU CUGAUGAGGCCGAAAGGCCGAA AGGAGCU 761 1754 CUCUGGGCUGAUGAGGCCGAAAGGCCGAA AGGGCAG 762

[0074] TABLE VI Human rel A Hairpin Ribozyme/Target Sequences nt. Seq IDSeq ID Position Hairpin Ribozyme sequence No. Substrate No. 90 UGAGGGGGAGAA GUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 763 GAACU GUU CCCCCUCA778 156 GCUGCUUG AGAA GCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 764GAGCA GCC CAAGCAGC 779 362 GCCAUCCC AGAA GUCCACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 765 GGACU GCC GGGAUGGC 780 413GUUCUGGA AGAA GUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 766 CCACA GUUUCCAGAAC 781 606 GAAGGACA AGAA GCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA767 CUGCC GCC UGUCCUUC 782 652 UUGAGCUC AGAA GUGUACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 768 ACACU GCC GAGCUCAA 783 695CCCACCGA AGAA GCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 769 CAGCU GCCUCGGUGGG 784 853 AGGCUGGG AGAA GCGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA770 ACGCA GAC CCCAGCCU 785 900 GGUCGGAA AGAA GCCGACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 771 CGGCG GCC UUCCGACC 786 955UGACGAUC AGAA GUAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 772 AUACA GACGAUCGUCA 787 1037 GUCGGUGG AGAA GCUGACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 773 CAGCG GAC CCACCGAC 788 1045GGCCGGGG AGAA GUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 774 CCACC GACCCCCGGCC 789 1410 CAUCAUCA AGAA GCAGACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 775 CUGCA GUU UGAUGAUG 790 1453ACAGCUGG AGAA GUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 776 GCACA GACCCAGCUGU 791 1471 GAUGCCAG AGAA GUGAACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 777 UCACA GAC CUGGCAUC 792

[0075] TABLE VII Mouse rel A Hairpin Ribozyme/Target Sequences nt. Seq.ID Seq. ID Position Hairpin Ribozyme sequence No. Substrate No. 137GUUGCUUC AGAA GUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 793 GAACA GCCGAAGCAAC 812 273 GAGAUUCG AGAA GUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA794 GAACA GUU CGAAUCUC 813 343 GCCAUCCC AGAA GUCCACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 795 GGACU GCC GGGAUGGC 814 366GGGCAGAG AGAA GCCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 796 AGGCU GACCUCUGCCC 815 633 UUGAGCUC AGAA GUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA797 ACACU GCC GAGCUCAA 816 676 CCCACCGA AGAA GCUCACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 798 GAGCU GCC UCGGUGGG 817 834AGGCUGGG AGAA GCGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 799 ACGCC GACCCCAGCCU 818 881 GAUCAGAA AGAA GCCG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA800 CGGCG GCC UUCUGAUC 819 1100 AGGUGUAG AGAA GCGGACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 801 CCGCA GCC CUACACCU 820 1205GGGCAGAG AGAA GUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 802 GCACC GUCCUCUGCCC 821 1361 GGGCUUCC AGAA GCGUACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 803 ACGCU GUC GGAAGCCC 822 1385CAGCAUCA AGAA GCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 804 CUGCA GUUUGAUGCUG 823 1431 ACUCCUGG AGAA GUGCACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 805 GCACA GAC CCAGGAGU 824 1449GAUGCCAG AGAA GUGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 806 UCACA GACCUGGCAUC 825 1802 AAGUCGGG AGAA GCUGACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 807 CAGCU GCC CCCGACUU 826 2009UGGCUCCA AGAA GUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 808 GGACA GACUGGAGCCA 827 2124 UGGUGUCG AGAA GCACACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 809 GUGCU GCC CGACACCA 828 2233AUUCUGAA AGAA GCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 810 UGGCC GCCUUCAGAAU 829 2354 UCAGUAAA AGAA GUCUACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA 811 AGACA GCC UUUACUGA 830

[0076]

1 830 11 nucleic acid single linear The letter “N” stands for any base.“H” represents nucleotide C, A, or U. 1 NNNNUHNNNN N 11 32 nucleic acidsingle linear The letter “N” stands for any base. 2 NNNNNCUGANGAGNNNNNNN NNNCGAAANN NN 32 14 nucleic acid single linear The letter “N”stands for any base. 3 NNNNNGUCNN NNNN 14 50 nucleic acid single linearThe letter “N” stands for any base. 4 NNNNNNAGAA NNNNACCAGA GAAACACACGUUGUGGUAUA UUACCUGGUA 50 85 nucleic acid single linear 5 UGGCCGGCAUGGUCCCAGCC UCCUCGCUGG CGCCGGCUGG GCAACAUUCC GAGGGGACCG 60 UCCCCUCGGUAAUGGCGAAU GGGAC 85 176 nucleic acid single linear 6 GGGAAAGCUUGCGAAGGGCG UCGUCGCCCC GAGCGGUAGU AAGCAGGGAA CUCACCUCCA 60 AUUUCAGUACUGAAAUUGUC GUAGCAGUUG ACUACUGUUA UGUGAUUGGU AGAGGCUAAG 120 UGACGGUAUUGGCGUAAGUC AGUAUUGCAG CACAGCACAA GCCCGCUUGC GAGAAU 176 15 base pairsnucleic acid single linear 7 AAUGGCUACA CAGGA 15 15 base pairs nucleicacid single linear 8 AGCUCCUACG UGGUG 15 15 base pairs nucleic acidsingle linear 9 CCUCCAUUGC GGACA 15 15 base pairs nucleic acid singlelinear 10 GAUCUGUUUC CCCUC 15 15 base pairs nucleic acid single linear11 AUCUGUUUCC CCUCA 15 15 base pairs nucleic acid single linear 12UUCCCCUCAU CUUUC 15 15 base pairs nucleic acid single linear 13CCCUCAUCUU UCCCU 15 15 base pairs nucleic acid single linear 14CUCAUCUUUC CCUCA 15 15 base pairs nucleic acid single linear 15UCAUCUUUCC CUCAG 15 15 base pairs nucleic acid single linear 16CAGGCUUCUG GGCCU 15 15 base pairs nucleic acid single linear 17GGGCCUUAUG UGGAG 15 15 base pairs nucleic acid single linear 18UGGAGAUCAU CGAAC 15 15 base pairs nucleic acid single linear 19AGAUCAUCGA ACAGC 15 15 base pairs nucleic acid single linear 20AUGCGAUUCC GCUAU 15 15 base pairs nucleic acid single linear 21UGCGAUUCCG CUAUA 15 15 base pairs nucleic acid single linear 22UUCCGCUAUA AAUGC 15 15 base pairs nucleic acid single linear 23GGGCGCUCAG CGGGC 15 15 base pairs nucleic acid single linear 24GCAGUAUUCC UGGCG 15 15 base pairs nucleic acid single linear 25CACAGAUACC ACCAA 15 15 base pairs nucleic acid single linear 26CCACCAUCAA GAUCA 15 15 base pairs nucleic acid single linear 27UCAAGAUCAA UGGCU 15 15 base pairs nucleic acid single linear 28AAUGGCUACA CAGGA 15 15 base pairs nucleic acid single linear 29UUCGAAUCUC CCUGG 15 15 base pairs nucleic acid single linear 30CGAAUCUCCC UGGUC 15 15 base pairs nucleic acid single linear 31CCCUGGUCAC CAAGG 15 15 base pairs nucleic acid single linear 32GGCCCCUCCU CCUGA 15 15 base pairs nucleic acid single linear 33UCCACCUCAC CGGCC 15 15 base pairs nucleic acid single linear 34CCGGCCUCAU CCACA 15 15 base pairs nucleic acid single linear 35AUGAACUUGU GGGGA 15 15 base pairs nucleic acid single linear 36AGAUCAUCGA ACAGC 15 15 base pairs nucleic acid single linear 37GAUGGCUACU AUGAG 15 15 base pairs nucleic acid single linear 38AUGGUCUCUC CGGAG 15 15 base pairs nucleic acid single linear 39GGCUACUAUG AGGCU 15 15 base pairs nucleic acid single linear 40CUGACCUCUG CCCAG 15 15 base pairs nucleic acid single linear 41GCAGUAUCCA UAGCU 15 15 base pairs nucleic acid single linear 42CCGCAGUAUC CAUAG 15 15 base pairs nucleic acid single linear 43CAUAGCUUCC AGAAC 15 15 base pairs nucleic acid single linear 44AUAGCUUCCA GAACC 15 15 base pairs nucleic acid single linear 45UGGGGAUCCA GUGUG 15 15 base pairs nucleic acid single linear 46GGCUCCUUUU CUCAA 15 15 base pairs nucleic acid single linear 47GCUCCUUUUC UCAAG 15 15 base pairs nucleic acid single linear 48CUCCUUUUCU CAAGC 15 15 base pairs nucleic acid single linear 49UCCUUUUCUC AAGCU 15 15 base pairs nucleic acid single linear 50UGGCCAUUGU GUUCC 15 15 base pairs nucleic acid single linear 51AUUGUGUUCC GGACU 15 15 base pairs nucleic acid single linear 52UUGUGUUCCG GACUC 15 15 base pairs nucleic acid single linear 53GACUCCUCCG UACGC 15 15 base pairs nucleic acid single linear 54CCUCCGUACG CCGAC 15 15 base pairs nucleic acid single linear 55CCAGGCUCCU GUUCG 15 15 base pairs nucleic acid single linear 56UUCGAGUCUC CAUGC 15 15 base pairs nucleic acid single linear 57CGAGUCUCCA UGCAG 15 15 base pairs nucleic acid single linear 58GCGGCCUUCU GAUCG 15 15 base pairs nucleic acid single linear 59CGGCCUUCUG AUCGC 15 15 base pairs nucleic acid single linear 60GCGAGCUCAG UGAGC 15 15 base pairs nucleic acid single linear 61AUGGAGUUCC AGUAC 15 15 base pairs nucleic acid single linear 62UGGAGUUCCA GUACU 15 15 base pairs nucleic acid single linear 63UUCCAGUACU UGCCA 15 15 base pairs nucleic acid single linear 64GCCUCAUCCA CAUGA 15 15 base pairs nucleic acid single linear 65AGAUGAUCGC CACCG 15 15 base pairs nucleic acid single linear 66CAGUACUUGC CAGAC 15 15 base pairs nucleic acid single linear 67ACCGGAUUGA AGAGA 15 15 base pairs nucleic acid single linear 68GAGACCUUCA AGAGU 15 15 base pairs nucleic acid single linear 69AGGACCUAUG AGACC 15 15 base pairs nucleic acid single linear 70GAGACCUUCA AGAGU 15 15 base pairs nucleic acid single linear 71AGACCUUCAA GAGUA 15 15 base pairs nucleic acid single linear 72AGAGUAUCAU GAAGA 15 15 base pairs nucleic acid single linear 73GAAGAGUCCU UUCAA 15 15 base pairs nucleic acid single linear 74GAGUCCUUUC AAUGG 15 15 base pairs nucleic acid single linear 75AGUCCUUUCA AUGGA 15 15 base pairs nucleic acid single linear 76GUCCUUUCAA UGGAC 15 15 base pairs nucleic acid single linear 77CCGGCCUCCA ACCCG 15 15 base pairs nucleic acid single linear 78UACACCUUGA UCCAA 15 15 base pairs nucleic acid single linear 79GGCGUAUUGC UGUGC 15 15 base pairs nucleic acid single linear 80UGUGCCUACC CGAAA 15 15 base pairs nucleic acid single linear 81AAGCCUUCCC GAAGU 15 15 base pairs nucleic acid single linear 82CGAAACUCAA CUUCU 15 15 base pairs nucleic acid single linear 83CUCAACUUCU GUCCC 15 15 base pairs nucleic acid single linear 84UCAACUUCUG UCCCC 15 15 base pairs nucleic acid single linear 85CUUCUGUCCC CAAGC 15 15 base pairs nucleic acid single linear 86CAGCCCUACA CCUUC 15 15 base pairs nucleic acid single linear 87GCCAUAUAGC CUUAC 15 15 base pairs nucleic acid single linear 88CAUCCCUCAG CACCA 15 15 base pairs nucleic acid single linear 89ACACCUUCCC AGCAU 15 15 base pairs nucleic acid single linear 90UCCAUCUCCA GCUUC 15 15 base pairs nucleic acid single linear 91UUUACUUUAG CGCGC 15 15 base pairs nucleic acid single linear 92CCAGCAUCCC UCAGC 15 15 base pairs nucleic acid single linear 93GCACCAUCAA CUUUG 15 15 base pairs nucleic acid single linear 94AUCAACUUUG AUGAG 15 15 base pairs nucleic acid single linear 95GAAGACUUCU CCUCC 15 15 base pairs nucleic acid single linear 96AAGACUUCUC CUCCA 15 15 base pairs nucleic acid single linear 97GACUUCUCCU CCAUU 15 15 base pairs nucleic acid single linear 98UUCUCCUCCA UUGCG 15 15 base pairs nucleic acid single linear 99CCUCCAUUGC GGACA 15 15 base pairs nucleic acid single linear 100AUGGACUUCU CUGCU 15 15 base pairs nucleic acid single linear 101UGGACUUCUC UGCUC 15 15 base pairs nucleic acid single linear 102GACUUCUCUG CUCUU 15 15 base pairs nucleic acid single linear 103UUUGAGUCAG AUCAG 15 15 base pairs nucleic acid single linear 104GUCAGAUCAG CUCCU 15 15 base pairs nucleic acid single linear 105AUCAGCUCCU AAGGU 15 15 base pairs nucleic acid single linear 106AGCUCCUAAG GUGCU 15 15 base pairs nucleic acid single linear 107CAGUGCUCCC AAGAG 15 15 base pairs nucleic acid single linear 108CCAGGCUCCU GUUCG 15 15 base pairs nucleic acid single linear 109AAGCCAUUAG CCAGC 15 15 base pairs nucleic acid single linear 110UUUGAGUCAG AUCAG 15 15 base pairs nucleic acid single linear 111AGCGAAUCCA GACCA 15 15 base pairs nucleic acid single linear 112AACCCCUUUC ACGUU 15 15 base pairs nucleic acid single linear 113ACCCCUUUCA CGUUC 15 15 base pairs nucleic acid single linear 114UUCACGUUCC UAUAG 15 15 base pairs nucleic acid single linear 115UCACGUUCCU AUAGA 15 15 base pairs nucleic acid single linear 116CGUUCCUAUA GAGGA 15 15 base pairs nucleic acid single linear 117UUCCUAUAGA GGAGC 15 15 base pairs nucleic acid single linear 118GGGGACUAUG ACUUG 15 15 base pairs nucleic acid single linear 119UGCGCCUCUG CUUCC 15 15 base pairs nucleic acid single linear 120CUCUGCUUCC AGGUG 15 15 base pairs nucleic acid single linear 121UCUGCUUCCA GGUGA 15 15 base pairs nucleic acid single linear 122AAGCCAUUAG CCAGC 15 15 base pairs nucleic acid single linear 123GGCCCCUCCU CCUGA 15 15 base pairs nucleic acid single linear 124CCCCUGUCCU CUCAC 15 15 base pairs nucleic acid single linear 125CUGUCCUCUC ACAUC 15 15 base pairs nucleic acid single linear 126GUCCCUUCCU CAGCC 15 15 base pairs nucleic acid single linear 127CCUUCCUCAG CCAUG 15 15 base pairs nucleic acid single linear 128UCCUGCUUCC AUCUC 15 15 base pairs nucleic acid single linear 129AUCCGAUUUU UGAUA 15 15 base pairs nucleic acid single linear 130CCGAUUUUUG AUAAC 15 15 base pairs nucleic acid single linear 131CGAUUUUUGA UAACC 15 15 base pairs nucleic acid single linear 132UGGCCAUUGU GUUCC 15 15 base pairs nucleic acid single linear 133CCGAGCUCAA GAUCU 15 15 base pairs nucleic acid single linear 134UCAAGAUCUG CCGAG 15 15 base pairs nucleic acid single linear 135CGGAACUCUG GGAGC 15 15 base pairs nucleic acid single linear 136GCUGCCUCGG UGGGG 15 15 base pairs nucleic acid single linear 137AUGAGAUCUU CUUGC 15 15 base pairs nucleic acid single linear 138GAGAUCUUCU UGCUG 15 15 base pairs nucleic acid single linear 139AGAUCUUCUU GCUGU 15 15 base pairs nucleic acid single linear 140UUCUCCUCCA UUGCG 15 15 base pairs nucleic acid single linear 141AAGACAUUGA GGUGU 15 15 base pairs nucleic acid single linear 142GAGGUGUAUU UCACG 15 15 base pairs nucleic acid single linear 143GGUGUAUUUC ACGGG 15 15 base pairs nucleic acid single linear 144GUGUAUUUCA CGGGA 15 15 base pairs nucleic acid single linear 145UGUAUUUCAC GGGAC 15 15 base pairs nucleic acid single linear 146CGAGGCUCCU UUUCU 15 15 base pairs nucleic acid single linear 147GAUGAGUUUU CCCCC 15 15 base pairs nucleic acid single linear 148AUGAGUUUUC CCCCA 15 15 base pairs nucleic acid single linear 149UGAGUUUUCC CCCAU 15 15 base pairs nucleic acid single linear 150AUGCUGUUAC CAUCA 15 15 base pairs nucleic acid single linear 151UGCUGUUACC AUCAG 15 15 base pairs nucleic acid single linear 152GGCCCCUCCU CCUGA 15 15 base pairs nucleic acid single linear 153GUCCCUUCCU CAGCC 15 15 base pairs nucleic acid single linear 154UUACCAUCAG GGCAG 15 15 base pairs nucleic acid single linear 155GGGAGUUUAG UCUGA 15 15 base pairs nucleic acid single linear 156CAGCCCUACA CCUUC 15 15 base pairs nucleic acid single linear 157CUGGCCUUAG CACCG 15 15 base pairs nucleic acid single linear 158GGUCCCUUCC UCAGC 15 15 base pairs nucleic acid single linear 159CCCAGCUCCU GCCCC 15 15 base pairs nucleic acid single linear 160CCAGCCUCCA GGCUC 15 15 base pairs nucleic acid single linear 161CCCAGCUCCU GCCCC 15 15 base pairs nucleic acid single linear 162CCAUGGUCCC UUCCU 15 15 base pairs nucleic acid single linear 163GUGGGCUCAG CUGCG 15 15 base pairs nucleic acid single linear 164AUGAGUUUUC CCCCA 15 15 base pairs nucleic acid single linear 165CUCCUGUUCG AGUCU 15 15 base pairs nucleic acid single linear 166CCCCAGUUCU AACCC 15 15 base pairs nucleic acid single linear 167CAGUUCUAAC CCCGG 15 15 base pairs nucleic acid single linear 168GGGUCCUCCC CAGUC 15 15 base pairs nucleic acid single linear 169CUUUUCUCAA GCUGA 15 15 base pairs nucleic acid single linear 170ACGCUGUCGG AAGCC 15 15 base pairs nucleic acid single linear 171CUGCAGUUUG AUGCU 15 15 base pairs nucleic acid single linear 172UGCAGUUUGA UGCUG 15 15 base pairs nucleic acid single linear 173GGGGCCUUGC UUGGC 15 15 base pairs nucleic acid single linear 174CCUUGCUUGG CAACA 15 15 base pairs nucleic acid single linear 175GGAGUGUUCA CAGAC 15 15 base pairs nucleic acid single linear 176GAGUGUUCAC AGACC 15 15 base pairs nucleic acid single linear 177CUGGCAUCUG UGGAC 15 15 base pairs nucleic acid single linear 178CUUCGGUAGG GAACU 15 15 base pairs nucleic acid single linear 179GACAACUCAG AGUUU 15 15 base pairs nucleic acid single linear 180UCAGAGUUUC AGCAG 15 15 base pairs nucleic acid single linear 181CAGAGUUUCA GCAGC 15 15 base pairs nucleic acid single linear 182AGAGUUUCAG CAGCU 15 15 base pairs nucleic acid single linear 183GGUGCAUCCC UGUGU 15 15 base pairs nucleic acid single linear 184AUGGAGUACC CUGAA 15 15 base pairs nucleic acid single linear 185UGAAGCUAUA ACUCG 15 15 base pairs nucleic acid single linear 186AAGCUAUAAC UCGCC 15 15 base pairs nucleic acid single linear 187UAUAACUCGC CUGGU 15 15 base pairs nucleic acid single linear 188CUCUCCUAGA GAGGG 15 15 base pairs nucleic acid single linear 189CCCAGCUCCU GCCCC 15 15 base pairs nucleic acid single linear 190UCCUGCUUCG GUAGG 15 15 base pairs nucleic acid single linear 191CGGGGCUUCC CAAUG 15 15 base pairs nucleic acid single linear 192CUGACCUCUG CCCAG 15 15 base pairs nucleic acid single linear 193CUCUGCUUCC AGGUG 15 15 base pairs nucleic acid single linear 194UCUGCUUCCA GGUGA 15 15 base pairs nucleic acid single linear 195CUCGCUUUCG GAGGU 15 15 base pairs nucleic acid single linear 196AAUGGCUCGU CUGUA 15 15 base pairs nucleic acid single linear 197GGCUCGUCUG UAGUG 15 15 base pairs nucleic acid single linear 198CGUCUGUAGU GCACG 15 15 base pairs nucleic acid single linear 199GAACUGUUCC CCCUC 15 15 base pairs nucleic acid single linear 200AACUGUUCCC CCUCA 15 15 base pairs nucleic acid single linear 201UCCCCCUCAU CUUCC 15 15 base pairs nucleic acid single linear 202CCCUCAUCUU CCCGG 15 15 base pairs nucleic acid single linear 203CUCAUCUUCC CGGCA 15 15 base pairs nucleic acid single linear 204UCAUCUUCCC GGCAG 15 15 base pairs nucleic acid single linear 205CAGGCCUCUG GCCCC 15 15 base pairs nucleic acid single linear 206GGCCCCUAUG UGGAG 15 15 base pairs nucleic acid single linear 207UGGAGAUCAU UGAGC 15 15 base pairs nucleic acid single linear 208AGAUCAUUGA GCAGC 15 15 base pairs nucleic acid single linear 209AUGCGCUUCC GCUAC 15 15 base pairs nucleic acid single linear 210UGCGCUUCCG CUACA 15 15 base pairs nucleic acid single linear 211UUCCGCUACA AGUGC 15 15 base pairs nucleic acid single linear 212GGGCGCUCCG CGGGC 15 15 base pairs nucleic acid single linear 213GCAGCAUCCC AGGCG 15 15 base pairs nucleic acid single linear 214CACAGAUACC ACCAA 15 15 base pairs nucleic acid single linear 215CCACCAUCAA GAUCA 15 15 base pairs nucleic acid single linear 216UCAAGAUCAA UGGCU 15 15 base pairs nucleic acid single linear 217AAUGGCUACA CAGGA 15 15 base pairs nucleic acid single linear 218UGCGCAUCUC CCUGG 15 15 base pairs nucleic acid single linear 219CGCAUCUCCC UGGUC 15 15 base pairs nucleic acid single linear 220CCCUGGUCAC CAAGG 15 15 base pairs nucleic acid single linear 221GGACCCUCCU CACCG 15 15 base pairs nucleic acid single linear 222CCCUCCUCAC CGGCC 15 15 base pairs nucleic acid single linear 223CCGGCCUCAC CCCCA 15 15 base pairs nucleic acid single linear 224ACGAGCUUGU AGGAA 15 15 base pairs nucleic acid single linear 225AGCUUGUAGG AAAGG 15 15 base pairs nucleic acid single linear 226GAUGGCUUCU AUGAG 15 15 base pairs nucleic acid single linear 227AUGGCUUCUA UGAGG 15 15 base pairs nucleic acid single linear 228GGCUUCUAUG AGGCU 15 15 base pairs nucleic acid single linear 229CUGAGCUCUG CCCGG 15 15 base pairs nucleic acid single linear 230GCUGCAUCCA CAGUU 15 15 base pairs nucleic acid single linear 231CCACAGUUUC CAGAA 15 15 base pairs nucleic acid single linear 232CACAGUUUCC AGAAC 15 15 base pairs nucleic acid single linear 233ACAGUUUCCA GAACC 15 15 base pairs nucleic acid single linear 234UGGGAAUCCA GUGUG 15 15 base pairs nucleic acid single linear 235GGCUCCUUUU CGCAA 15 15 base pairs nucleic acid single linear 236GCUCCUUUUC GCAAG 15 15 base pairs nucleic acid single linear 237CUCCUUUUCG CAAGC 15 15 base pairs nucleic acid single linear 238UCCUUUUCGC AAGCU 15 15 base pairs nucleic acid single linear 239UGGCCAUUGU GUUCC 15 15 base pairs nucleic acid single linear 240AUUGUGUUCC GGACC 15 15 base pairs nucleic acid single linear 241UUGUGUUCCG GACCC 15 15 base pairs nucleic acid single linear 242GACCCCUCCC UACGC 15 15 base pairs nucleic acid single linear 243CCUCCCUACG CAGAC 15 15 base pairs nucleic acid single linear 244GCAGGCUCCU GUGCG 15 15 base pairs nucleic acid single linear 245UGCGUGUCUC CAUGC 15 15 base pairs nucleic acid single linear 246CGUGUCUCCA UGCAG 15 15 base pairs nucleic acid single linear 247GCGGCCUUCC GACCG 15 15 base pairs nucleic acid single linear 248CGGCCUUCCG ACCGG 15 15 base pairs nucleic acid single linear 249GGGAGCUCAG UGAGC 15 15 base pairs nucleic acid single linear 250AUGGAAUUCC AGUAC 15 15 base pairs nucleic acid single linear 251UGGAAUUCCA GUACC 15 15 base pairs nucleic acid single linear 252UUCCAGUACC UGCCA 15 15 base pairs nucleic acid single linear 253GCCAGAUACA GACGA 15 15 base pairs nucleic acid single linear 254AGACGAUCGU CACCG 15 15 base pairs nucleic acid single linear 255CGAUCGUCAC CGGAU 15 15 base pairs nucleic acid single linear 256ACCGGAUUGA GGAGA 15 15 base pairs nucleic acid single linear 257GAAACGUAAA AGGAC 15 15 base pairs nucleic acid single linear 258AGGACAUAUG AGACC 15 15 base pairs nucleic acid single linear 259GAGACCUUCA AGAGC 15 15 base pairs nucleic acid single linear 260AGACCUUCAA GAGCA 15 15 base pairs nucleic acid single linear 261AGAGCAUCAU GAAGA 15 15 base pairs nucleic acid single linear 262GAAGAGUCCU UUCAG 15 15 base pairs nucleic acid single linear 263GAGUCCUUUC AGCGG 15 15 base pairs nucleic acid single linear 264AGUCCUUUCA GCGGA 15 15 base pairs nucleic acid single linear 265GUCCUUUCAG CGGAC 15 15 base pairs nucleic acid single linear 266CCGGCCUCCA CCUCG 15 15 base pairs nucleic acid single linear 267UCCACCUCGA CGCAU 15 15 base pairs nucleic acid single linear 268GACGCAUUGC UGUGC 15 15 base pairs nucleic acid single linear 269UGUGCCUUCC CGCAG 15 15 base pairs nucleic acid single linear 270GUGCCUUCCC GCAGC 15 15 base pairs nucleic acid single linear 271CGCAGCUCAG CUUCU 15 15 base pairs nucleic acid single linear 272CUCAGCUUCU GUCCC 15 15 base pairs nucleic acid single linear 273UCAGCUUCUG UCCCC 15 15 base pairs nucleic acid single linear 274CUUCUGUCCC CAAGC 15 15 base pairs nucleic acid single linear 275CAGCCCUAUC CCUUU 15 15 base pairs nucleic acid single linear 276GCCCUAUCCC UUUAC 15 15 base pairs nucleic acid single linear 277UAUCCCUUUA CGUCA 15 15 base pairs nucleic acid single linear 278AUCCCUUUAC GUCAU 15 15 base pairs nucleic acid single linear 279UCCCUUUACG UCAUC 15 15 base pairs nucleic acid single linear 280UUUACGUCAU CCCUG 15 15 base pairs nucleic acid single linear 281ACGUCAUCCC UGAGC 15 15 base pairs nucleic acid single linear 282GCACCAUCAA CUAUG 15 15 base pairs nucleic acid single linear 283AUCAACUAUG AUGAG 15 15 base pairs nucleic acid single linear 284GAAGACUUCU CCUCC 15 15 base pairs nucleic acid single linear 285AAGACUUCUC CUCCA 15 15 base pairs nucleic acid single linear 286GACUUCUCCU CCAUU 15 15 base pairs nucleic acid single linear 287UUCUCCUCCA UUGCG 15 15 base pairs nucleic acid single linear 288CCUCCAUUGC GGACA 15 15 base pairs nucleic acid single linear 289AUGGACUUCU CAGCC 15 15 base pairs nucleic acid single linear 290UGGACUUCUC AGCCC 15 15 base pairs nucleic acid single linear 291GACUUCUCAG CCCUG 15 15 base pairs nucleic acid single linear 292GCUGAGUCAG AUCAG 15 15 base pairs nucleic acid single linear 293GUCAGAUCAG CUCCU 15 15 base pairs nucleic acid single linear 294AUCAGCUCCU AAGGG 15 15 base pairs nucleic acid single linear 295AGCUCCUAAG GGGGU 15 15 base pairs nucleic acid single linear 296CUGCCCUCCC CAGAG 15 15 base pairs nucleic acid single linear 297GCAGGCUAUC AGUCA 15 15 base pairs nucleic acid single linear 298AGGCUAUCAG UCAGC 15 15 base pairs nucleic acid single linear 299UAUCAGUCAG CGCAU 15 15 base pairs nucleic acid single linear 300AGCGCAUCCA GACCA 15 15 base pairs nucleic acid single linear 301AACCCCUUCC AAGUU 15 15 base pairs nucleic acid single linear 302ACCCCUUCCA AGUUC 15 15 base pairs nucleic acid single linear 303UCCAAGUUCC UAUAG 15 15 base pairs nucleic acid single linear 304CCAAGUUCCU AUAGA 15 15 base pairs nucleic acid single linear 305AGUUCCUAUA GAAGA 15 15 base pairs nucleic acid single linear 306UUCCUAUAGA AGAGC 15 15 base pairs nucleic acid single linear 307GGGGACUACG ACCUG 15 15 base pairs nucleic acid single linear 308UGCGGCUCUG CUUCC 15 15 base pairs nucleic acid single linear 309CUCUGCUUCC AGGUG 15 15 base pairs nucleic acid single linear 310UCUGCUUCCA GGUGA 15 15 base pairs nucleic acid single linear 311GACCCAUCAG GCAGG 15 15 base pairs nucleic acid single linear 312GGCCCCUCCG CCUGC 15 15 base pairs nucleic acid single linear 313CGCCUGUCCU UCCUC 15 15 base pairs nucleic acid single linear 314CUGUCCUUCC UCAUC 15 15 base pairs nucleic acid single linear 315UGUCCUUCCU CAUCC 15 15 base pairs nucleic acid single linear 316CCUUCCUCAU CCCAU 15 15 base pairs nucleic acid single linear 317UCCUCAUCCC AUCUU 15 15 base pairs nucleic acid single linear 318AUCCCAUCUU UGACA 15 15 base pairs nucleic acid single linear 319CCCAUCUUUG ACAAU 15 15 base pairs nucleic acid single linear 320CCAUCUUUGA CAAUC 15 15 base pairs nucleic acid single linear 321UGACAAUCGU GCCCC 15 15 base pairs nucleic acid single linear 322CCGAGCUCAA GAUCU 15 15 base pairs nucleic acid single linear 323UCAAGAUCUG CCGAG 15 15 base pairs nucleic acid single linear 324CGAAACUCUG GCAGC 15 15 base pairs nucleic acid single linear 325GCUGCCUCGG UGGGG 15 15 base pairs nucleic acid single linear 326AUGAGAUCUU CCUAC 15 15 base pairs nucleic acid single linear 327GAGAUCUUCC UACUG 15 15 base pairs nucleic acid single linear 328AGAUCUUCCU ACUGU 15 15 base pairs nucleic acid single linear 329UCUUCCUACU GUGUG 15 15 base pairs nucleic acid single linear 330AGGACAUUGA GGUGU 15 15 base pairs nucleic acid single linear 331GAGGUGUAUU UCACG 15 15 base pairs nucleic acid single linear 332GGUGUAUUUC ACGGG 15 15 base pairs nucleic acid single linear 333GUGUAUUUCA CGGGA 15 15 base pairs nucleic acid single linear 334UGUAUUUCAC GGGAC 15 15 base pairs nucleic acid single linear 335CGAGGCUCCU UUUCG 15 15 base pairs nucleic acid single linear 336GAUGAGUUUC CCACC 15 15 base pairs nucleic acid single linear 337AUGAGUUUCC CACCA 15 15 base pairs nucleic acid single linear 338UGAGUUUCCC ACCAU 15 15 base pairs nucleic acid single linear 339AUGGUGUUUC CUUCU 15 15 base pairs nucleic acid single linear 340UGGUGUUUCC UUCUG 15 15 base pairs nucleic acid single linear 341GGUGUUUCCU UCUGG 15 15 base pairs nucleic acid single linear 342GUUUCCUUCU GGGCA 15 15 base pairs nucleic acid single linear 343UUUCCUUCUG GGCAG 15 15 base pairs nucleic acid single linear 344GGCAGAUCAG CCAGG 15 15 base pairs nucleic acid single linear 345CAGGCCUCGG CCUUG 15 15 base pairs nucleic acid single linear 346UCGGCCUUGG CCCCG 15 15 base pairs nucleic acid single linear 347GGCCCCUCCC CAAGU 15 15 base pairs nucleic acid single linear 348CCCAAGUCCU GCCCC 15 15 base pairs nucleic acid single linear 349CCAGGCUCCA GCCCC 15 15 base pairs nucleic acid single linear 350CCCUGCUCCA GCCAU 15 15 base pairs nucleic acid single linear 351CCAUGGUAUC AGCUC 15 15 base pairs nucleic acid single linear 352AUGGUAUCAG CUCUG 15 15 base pairs nucleic acid single linear 353AUCAGCUCUG GCCCA 15 15 base pairs nucleic acid single linear 354CCCCUGUCCC AGUCC 15 15 base pairs nucleic acid single linear 355UCCCAGUCCU AGCCC 15 15 base pairs nucleic acid single linear 356CAGUCCUAGC CCCAG 15 15 base pairs nucleic acid single linear 357AGGCCCUCCU CAGGC 15 15 base pairs nucleic acid single linear 358CCCUCCUCAG GCUGU 15 15 base pairs nucleic acid single linear 359ACGCUGUCAG AGGCC 15 15 base pairs nucleic acid single linear 360CUGCAGUUUG AUGAU 15 15 base pairs nucleic acid single linear 361UGCAGUUUGA UGAUG 15 15 base pairs nucleic acid single linear 362GGGGCCUUGC UUGGC 15 15 base pairs nucleic acid single linear 363CCUUGCUUGG CAACA 15 15 base pairs nucleic acid single linear 364GCUGUGUUCA CAGAC 15 15 base pairs nucleic acid single linear 365CUGUGUUCAC AGACC 15 15 base pairs nucleic acid single linear 366CUGGCAUCCG UCGAC 15 15 base pairs nucleic acid single linear 367CAUCCGUCGA CAACU 15 15 base pairs nucleic acid single linear 368GACAACUCCG AGUUU 15 15 base pairs nucleic acid single linear 369UCCGAGUUUC AGCAG 15 15 base pairs nucleic acid single linear 370CCGAGUUUCA GCAGC 15 15 base pairs nucleic acid single linear 371CGAGUUUCAG CAGCU 15 15 base pairs nucleic acid single linear 372AGGGCAUACC UGUGG 15 15 base pairs nucleic acid single linear 373AUGGAGUACC CUGAG 15 15 base pairs nucleic acid single linear 374UGAGGCUAUA ACUCG 15 15 base pairs nucleic acid single linear 375AGGCUAUAAC UCGCC 15 15 base pairs nucleic acid single linear 376UAUAACUCGC CUAGU 15 15 base pairs nucleic acid single linear 377CUCGCCUAGU GACAG 15 15 base pairs nucleic acid single linear 378CCCAGCUCCU GCUCC 15 15 base pairs nucleic acid single linear 379UCCUGCUCCA CUGGG 15 15 base pairs nucleic acid single linear 380CGGGGCUCCC CAAUG 15 15 base pairs nucleic acid single linear 381AUGGCCUCCU UUCAG 15 15 base pairs nucleic acid single linear 382GCCUCCUUUC AGGAG 15 15 base pairs nucleic acid single linear 383CCUCCUUUCA GGAGA 15 15 base pairs nucleic acid single linear 384CUCCUUUCAG GAGAU 15 36 base pairs nucleic acid single linear 385UCCUGUGCUG AUGAGGCCGA AAGGCCGAAA GCCAUU 36 36 base pairs nucleic acidsingle linear 386 CACCACGCUG AUGAGGCCGA AAGGCCGAAA GGAGCU 36 36 basepairs nucleic acid single linear 387 UGUCCGCCUG AUGAGGCCGA AAGGCCGAAAUGGAGG 36 36 base pairs nucleic acid single linear 388 GAGGGGACUGAUGAGGCCGA AAGGCCGAAA CAGAUC 36 36 base pairs nucleic acid single linear389 UGAGGGGCUG AUGAGGCCGA AAGGCCGAAA ACAGAU 36 36 base pairs nucleicacid single linear 390 GAAAGAUCUG AUGAGGCCGA AAGGCCGAAA GGGGAA 36 36base pairs nucleic acid single linear 391 AGGGAAACUG AUGAGGCCGAAAGGCCGAAA UGAGGG 36 36 base pairs nucleic acid single linear 392UGAGGGACUG AUGAGGCCGA AAGGCCGAAA GAUGAG 36 36 base pairs nucleic acidsingle linear 393 CUGAGGGCUG AUGAGGCCGA AAGGCCGAAA AGAUGA 36 36 basepairs nucleic acid single linear 394 AGGCCCACUG AUGAGGCCGA AAGGCCGAAAAGCCUG 36 36 base pairs nucleic acid single linear 395 CUCCACACUGAUGAGGCCGA AAGGCCGAAA AGGCCC 36 36 base pairs nucleic acid single linear396 GUUCGAUCUG AUGAGGCCGA AAGGCCGAAA UCUCCA 36 36 base pairs nucleicacid single linear 397 GCUGUUCCUG AUGAGGCCGA AAGGCCGAAA UGAUCU 36 36base pairs nucleic acid single linear 398 AUAGCGGCUG AUGAGGCCGAAAGGCCGAAA UCGCAU 36 36 base pairs nucleic acid single linear 399UAUAGCGCUG AUGAGGCCGA AAGGCCGAAA AUCGCA 36 36 base pairs nucleic acidsingle linear 400 GCAUUUACUG AUGAGGCCGA AAGGCCGAAA GCGGAA 36 36 basepairs nucleic acid single linear 401 GCCCGCUCUG AUGAGGCCGA AAGGCCGAAAGCGCCC 36 36 base pairs nucleic acid single linear 402 CGCCAGGCUGAUGAGGCCGA AAGGCCGAAA UACUGC 36 36 base pairs nucleic acid single linear403 UUGGUGGCUG AUGAGGCCGA AAGGCCGAAA UCUGUG 36 36 base pairs nucleicacid single linear 404 UGAUCUUCUG AUGAGGCCGA AAGGCCGAAA UGGUGG 36 36base pairs nucleic acid single linear 405 AGCCAUUCUG AUGAGGCCGAAAGGCCGAAA UCUUGA 36 36 base pairs nucleic acid single linear 406UCCUGUGCUG AUGAGGCCGA AAGGCCGAAA GCCAUU 36 36 base pairs nucleic acidsingle linear 407 CCAGGGACUG AUGAGGCCGA AAGGCCGAAA UUCGAA 36 36 basepairs nucleic acid single linear 408 GACCAGGCUG AUGAGGCCGA AAGGCCGAAAGAUUCG 36 36 base pairs nucleic acid single linear 409 CCUUGGUCUGAUGAGGCCGA AAGGCCGAAA CCAGGG 36 36 base pairs nucleic acid single linear410 UCAGGAGCUG AUGAGGCCGA AAGGCCGAAA GGGGCC 36 36 base pairs nucleicacid single linear 411 GGCCGGUCUG AUGAGGCCGA AAGGCCGAAA GGUGGA 36 36base pairs nucleic acid single linear 412 UGUGGAUCUG AUGAGGCCGAAAGGCCGAAA GGCCGG 36 36 base pairs nucleic acid single linear 413UCCCCACCUG AUGAGGCCGA AAGGCCGAAA GUUCAU 36 36 base pairs nucleic acidsingle linear 414 GCUGUUCCUG AUGAGGCCGA AAGGCCGAAA UGAUCU 36 36 basepairs nucleic acid single linear 415 CUCAUAGCUG AUGAGGCCGA AAGGCCGAAAGCCAUC 36 36 base pairs nucleic acid single linear 416 CUCCGGACUGAUGAGGCCGA AAGGCCGAAA GACCAU 36 36 base pairs nucleic acid single linear417 AGCCUCACUG AUGAGGCCGA AAGGCCGAAA GUAGCC 36 36 base pairs nucleicacid single linear 418 CUGGGCACUG AUGAGGCCGA AAGGCCGAAA GGUCAG 36 36base pairs nucleic acid single linear 419 AGCUAUGCUG AUGAGGCCGAAAGGCCGAAA UACUGC 36 36 base pairs nucleic acid single linear 420CUAUGGACUG AUGAGGCCGA AAGGCCGAAA CUGCGG 36 36 base pairs nucleic acidsingle linear 421 GUUCUGGCUG AUGAGGCCGA AAGGCCGAAA GCUAUG 36 36 basepairs nucleic acid single linear 422 GGUUCUGCUG AUGAGGCCGA AAGGCCGAAAAGCUAU 36 36 base pairs nucleic acid single linear 423 CACACUGCUGAUGAGGCCGA AAGGCCGAAA UCCCCA 36 36 base pairs nucleic acid single linear424 CGAACAGCUG AUGAGGCCGA AAGGCCGAAA GCCUGG 36 36 base pairs nucleicacid single linear 425 GCUGGCUCUG AUGAGGCCGA AAGGCCGAAA UGGCUU 36 36base pairs nucleic acid single linear 426 CUGAUCUCUG AUGAGGCCGAAAGGCCGAAA CUCAAA 36 36 base pairs nucleic acid single linear 427UGGUCUGCUG AUGAGGCCGA AAGGCCGAAA UUCGCU 36 36 base pairs nucleic acidsingle linear 428 AACGUGACUG AUGAGGCCGA AAGGCCGAAA GGGGUU 36 36 basepairs nucleic acid single linear 429 GAACGUGCUG AUGAGGCCGA AAGGCCGAAAAGGGGU 36 36 base pairs nucleic acid single linear 430 CUAUAGGCUGAUGAGGCCGA AAGGCCGAAA CGUGAA 36 36 base pairs nucleic acid single linear431 UCUAUAGCUG AUGAGGCCGA AAGGCCGAAA ACGUGA 36 36 base pairs nucleicacid single linear 432 UCCUCUACUG AUGAGGCCGA AAGGCCGAAA GGAACG 36 36base pairs nucleic acid single linear 433 GCUCCUCCUG AUGAGGCCGAAAGGCCGAAA UAGGAA 36 36 base pairs nucleic acid single linear 434CAAGUCACUG AUGAGGCCGA AAGGCCGAAA GUCCCC 36 36 base pairs nucleic acidsingle linear 435 GGAAGCACUG AUGAGGCCGA AAGGCCGAAA GGCGCA 36 36 basepairs nucleic acid single linear 436 CACCUGGCUG AUGAGGCCGA AAGGCCGAAAGCAGAG 36 36 base pairs nucleic acid single linear 437 UCACCUGCUGAUGAGGCCGA AAGGCCGAAA AGCAGA 36 36 base pairs nucleic acid single linear438 GCUGGCUCUG AUGAGGCCGA AAGGCCGAAA UGGCUU 36 36 base pairs nucleicacid single linear 439 UCAGGAGCUG AUGAGGCCGA AAGGCCGAAA GGGGCC 36 36base pairs nucleic acid single linear 440 GUGAGAGCUG AUGAGGCCGAAAGGCCGAAA CAGGGG 36 36 base pairs nucleic acid single linear 441GAUGUGACUG AUGAGGCCGA AAGGCCGAAA GGACAG 36 36 base pairs nucleic acidsingle linear 442 GGCUGAGCUG AUGAGGCCGA AAGGCCGAAA AGGGAC 36 36 basepairs nucleic acid single linear 443 CAUGGCUCUG AUGAGGCCGA AAGGCCGAAAGGAAGG 36 36 base pairs nucleic acid single linear 444 GAGAUGGCUGAUGAGGCCGA AAGGCCGAAA GCAGGA 36 36 base pairs nucleic acid single linear445 UAUCAAACUG AUGAGGCCGA AAGGCCGAAA UCGGAU 36 36 base pairs nucleicacid single linear 446 GUUAUCACUG AUGAGGCCGA AAGGCCGAAA AAUCGG 36 36base pairs nucleic acid single linear 447 GGUUAUCCUG AUGAGGCCGAAAGGCCGAAA AAAUCG 36 36 base pairs nucleic acid single linear 448GGAACACCUG AUGAGGCCGA AAGGCCGAAA UGGCCA 36 36 base pairs nucleic acidsingle linear 449 AGAUCUUCUG AUGAGGCCGA AAGGCCGAAA GCUCGG 36 36 basepairs nucleic acid single linear 450 CUCGGCACUG AUGAGGCCGA AAGGCCGAAAUCUUGA 36 36 base pairs nucleic acid single linear 451 GCUCCCACUGAUGAGGCCGA AAGGCCGAAA GUUCCG 36 36 base pairs nucleic acid single linear452 CCCCACCCUG AUGAGGCCGA AAGGCCGAAA GGCAGC 36 36 base pairs nucleicacid single linear 453 GCAAGAACUG AUGAGGCCGA AAGGCCGAAA UCUCAU 36 36base pairs nucleic acid single linear 454 CAGCAAGCUG AUGAGGCCGAAAGGCCGAAA GAUCUC 36 36 base pairs nucleic acid single linear 455ACAGCAACUG AUGAGGCCGA AAGGCCGAAA AGAUCU 36 36 base pairs nucleic acidsingle linear 456 CGCAAUGCUG AUGAGGCCGA AAGGCCGAAA GGAGAA 36 36 basepairs nucleic acid single linear 457 ACACCUCCUG AUGAGGCCGA AAGGCCGAAAUGUCUU 36 36 base pairs nucleic acid single linear 458 CGUGAAACUGAUGAGGCCGA AAGGCCGAAA CACCUC 36 36 base pairs nucleic acid single linear459 CCCGUGACUG AUGAGGCCGA AAGGCCGAAA UACACC 36 36 base pairs nucleicacid single linear 460 UCCCGUGCUG AUGAGGCCGA AAGGCCGAAA AUACAC 36 36base pairs nucleic acid single linear 461 GUCCCGUCUG AUGAGGCCGAAAGGCCGAAA AAUACA 36 36 base pairs nucleic acid single linear 462AGAAAAGCUG AUGAGGCCGA AAGGCCGAAA GCCUCG 36 36 base pairs nucleic acidsingle linear 463 UUGAGAACUG AUGAGGCCGA AAGGCCGAAA GGAGCC 36 36 basepairs nucleic acid single linear 464 CUUGAGACUG AUGAGGCCGA AAGGCCGAAAAGGAGC 36 36 base pairs nucleic acid single linear 465 GCUUGAGCUGAUGAGGCCGA AAGGCCGAAA AAGGAG 36 36 base pairs nucleic acid single linear466 AGCUUGACUG AUGAGGCCGA AAGGCCGAAA AAAGGA 36 36 base pairs nucleicacid single linear 467 GGAACACCUG AUGAGGCCGA AAGGCCGAAA UGGCCA 36 36base pairs nucleic acid single linear 468 AGUCCGGCUG AUGAGGCCGAAAGGCCGAAA CACAAU 36 36 base pairs nucleic acid single linear 469GAGUCCGCUG AUGAGGCCGA AAGGCCGAAA ACACAA 36 36 base pairs nucleic acidsingle linear 470 GCGUACGCUG AUGAGGCCGA AAGGCCGAAA GGAGUC 36 36 basepairs nucleic acid single linear 471 GUCGGCGCUG AUGAGGCCGA AAGGCCGAAACGGAGG 36 36 base pairs nucleic acid single linear 472 CGAACAGCUGAUGAGGCCGA AAGGCCGAAA GCCUGG 36 36 base pairs nucleic acid single linear473 GCAUGGACUG AUGAGGCCGA AAGGCCGAAA CUCGAA 36 36 base pairs nucleicacid single linear 474 CUGCAUGCUG AUGAGGCCGA AAGGCCGAAA GACUCG 36 36base pairs nucleic acid single linear 475 CGAUCAGCUG AUGAGGCCGAAAGGCCGAAA GGCCGC 36 36 base pairs nucleic acid single linear 476GCGAUCACUG AUGAGGCCGA AAGGCCGAAA AGGCCG 36 36 base pairs nucleic acidsingle linear 477 GCUCACUCUG AUGAGGCCGA AAGGCCGAAA GCUCGC 36 36 basepairs nucleic acid single linear 478 GUACUGGCUG AUGAGGCCGA AAGGCCGAAACUCCAU 36 36 base pairs nucleic acid single linear 479 AGUACUGCUGAUGAGGCCGA AAGGCCGAAA ACUCCA 36 36 base pairs nucleic acid single linear480 UGGCAAGCUG AUGAGGCCGA AAGGCCGAAA CUGGAA 36 36 base pairs nucleicacid single linear 481 UCAUGUGCUG AUGAGGCCGA AAGGCCGAAA UGAGGC 36 36base pairs nucleic acid single linear 482 CGGUGGCCUG AUGAGGCCGAAAGGCCGAAA UCAUCU 36 36 base pairs nucleic acid single linear 483GUCUGGCCUG AUGAGGCCGA AAGGCCGAAA GUACUG 36 36 base pairs nucleic acidsingle linear 484 UCUCUUCCUG AUGAGGCCGA AAGGCCGAAA UCCGGU 36 36 basepairs nucleic acid single linear 485 ACUCUUGCUG AUGAGGCCGA AAGGCCGAAAGGUCUC 36 36 base pairs nucleic acid single linear 486 GGUCUCACUGAUGAGGCCGA AAGGCCGAAA GGUCCU 36 36 base pairs nucleic acid single linear487 ACUCUUGCUG AUGAGGCCGA AAGGCCGAAA GGUCUC 36 36 base pairs nucleicacid single linear 488 UACUCUUCUG AUGAGGCCGA AAGGCCGAAA AGGUCU 36 36base pairs nucleic acid single linear 489 UCUUCAUCUG AUGAGGCCGAAAGGCCGAAA UACUCU 36 36 base pairs nucleic acid single linear 490UUGAAAGCUG AUGAGGCCGA AAGGCCGAAA CUCUUC 36 36 base pairs nucleic acidsingle linear 491 CCAUUGACUG AUGAGGCCGA AAGGCCGAAA GGACUC 36 36 basepairs nucleic acid single linear 492 UCCAUUGCUG AUGAGGCCGA AAGGCCGAAAAGGACU 36 36 base pairs nucleic acid single linear 493 GUCCAUUCUGAUGAGGCCGA AAGGCCGAAA AAGGAC 36 36 base pairs nucleic acid single linear494 CGGGUUGCUG AUGAGGCCGA AAGGCCGAAA GGCCGG 36 36 base pairs nucleicacid single linear 495 UUGGAUCCUG AUGAGGCCGA AAGGCCGAAA GGUGUA 36 36base pairs nucleic acid single linear 496 GCACAGCCUG AUGAGGCCGAAAGGCCGAAA UACGCC 36 36 base pairs nucleic acid single linear 497UUUCGGGCUG AUGAGGCCGA AAGGCCGAAA GGCACA 36 36 base pairs nucleic acidsingle linear 498 ACUUCGGCUG AUGAGGCCGA AAGGCCGAAA AGGCUU 36 36 basepairs nucleic acid single linear 499 AGAAGUUCUG AUGAGGCCGA AAGGCCGAAAGUUUCG 36 36 base pairs nucleic acid single linear 500 GGGACAGCUGAUGAGGCCGA AAGGCCGAAA GUUGAG 36 36 base pairs nucleic acid single linear501 GGGGACACUG AUGAGGCCGA AAGGCCGAAA AGUUGA 36 36 base pairs nucleicacid single linear 502 GCUUGGGCUG AUGAGGCCGA AAGGCCGAAA CAGAAG 36 36base pairs nucleic acid single linear 503 GAAGGUGCUG AUGAGGCCGAAAGGCCGAAA GGGCUG 36 36 base pairs nucleic acid single linear 504GUAAGGCCUG AUGAGGCCGA AAGGCCGAAA UAUGGC 36 36 base pairs nucleic acidsingle linear 505 UGGUGCUCUG AUGAGGCCGA AAGGCCGAAA GGGAUG 36 36 basepairs nucleic acid single linear 506 AUGCUGGCUG AUGAGGCCGA AAGGCCGAAAAGGUGU 36 36 base pairs nucleic acid single linear 507 GAAGCUGCUGAUGAGGCCGA AAGGCCGAAA GAUGGA 36 36 base pairs nucleic acid single linear508 GCGCGCUCUG AUGAGGCCGA AAGGCCGAAA AGUAAA 36 36 base pairs nucleicacid single linear 509 GCUGAGGCUG AUGAGGCCGA AAGGCCGAAA UGCUGG 36 36base pairs nucleic acid single linear 510 CAAAGUUCUG AUGAGGCCGAAAGGCCGAAA UGGUGC 36 36 base pairs nucleic acid single linear 511CUCAUCACUG AUGAGGCCGA AAGGCCGAAA GUUGAU 36 36 base pairs nucleic acidsingle linear 512 GGGGGAACUG AUGAGGCCGA AAGGCCGAAA CUCAUC 36 36 basepairs nucleic acid single linear 513 UGGGGGACUG AUGAGGCCGA AAGGCCGAAAACUCAU 36 36 base pairs nucleic acid single linear 514 AUGGGGGCUGAUGAGGCCGA AAGGCCGAAA AACUCA 36 36 base pairs nucleic acid single linear515 UGAUGGUCUG AUGAGGCCGA AAGGCCGAAA CAGCAU 36 36 base pairs nucleicacid single linear 516 CUGAUGGCUG AUGAGGCCGA AAGGCCGAAA ACAGCA 36 36base pairs nucleic acid single linear 517 UCAGGAGCUG AUGAGGCCGAAAGGCCGAAA GGGGCC 36 36 base pairs nucleic acid single linear 518GGCUGAGCUG AUGAGGCCGA AAGGCCGAAA AGGGAC 36 36 base pairs nucleic acidsingle linear 519 CUGCCCUCUG AUGAGGCCGA AAGGCCGAAA UGGUAA 36 36 basepairs nucleic acid single linear 520 UCAGACUCUG AUGAGGCCGA AAGGCCGAAAACUCCC 36 36 base pairs nucleic acid single linear 521 GAAGGUGCUGAUGAGGCCGA AAGGCCGAAA GGGCUG 36 36 base pairs nucleic acid single linear522 CGGUGCUCUG AUGAGGCCGA AAGGCCGAAA GGCCAG 36 36 base pairs nucleicacid single linear 523 GCUGAGGCUG AUGAGGCCGA AAGGCCGAAA GGGACC 36 36base pairs nucleic acid single linear 524 GGGGCAGCUG AUGAGGCCGAAAGGCCGAAA GCUGGG 36 36 base pairs nucleic acid single linear 525GAGCCUGCUG AUGAGGCCGA AAGGCCGAAA GGCUGG 36 36 base pairs nucleic acidsingle linear 526 GGGGCAGCUG AUGAGGCCGA AAGGCCGAAA GCUGGG 36 36 basepairs nucleic acid single linear 527 AGGAAGGCUG AUGAGGCCGA AAGGCCGAAACCAUGG 36 36 base pairs nucleic acid single linear 528 CGCAGCUCUGAUGAGGCCGA AAGGCCGAAA GCCCAC 36 36 base pairs nucleic acid single linear529 UGGGGGACUG AUGAGGCCGA AAGGCCGAAA ACUCAU 36 36 base pairs nucleicacid single linear 530 AGACUCGCUG AUGAGGCCGA AAGGCCGAAA CAGGAG 36 36base pairs nucleic acid single linear 531 GGGUUAGCUG AUGAGGCCGAAAGGCCGAAA CUGGGG 36 36 base pairs nucleic acid single linear 532CCGGGGUCUG AUGAGGCCGA AAGGCCGAAA GAACUG 36 36 base pairs nucleic acidsingle linear 533 GACUGGGCUG AUGAGGCCGA AAGGCCGAAA GGACCC 36 36 basepairs nucleic acid single linear 534 UCAGCUUCUG AUGAGGCCGA AAGGCCGAAAGAAAAG 36 36 base pairs nucleic acid single linear 535 GGCUUCCCUGAUGAGGCCGA AAGGCCGAAA CAGCGU 36 36 base pairs nucleic acid single linear536 AGCAUCACUG AUGAGGCCGA AAGGCCGAAA CUGCAG 36 36 base pairs nucleicacid single linear 537 CAGCAUCCUG AUGAGGCCGA AAGGCCGAAA ACUGCA 36 36base pairs nucleic acid single linear 538 GCCAAGCCUG AUGAGGCCGAAAGGCCGAAA GGCCCC 36 36 base pairs nucleic acid single linear 539UGUUGCCCUG AUGAGGCCGA AAGGCCGAAA GCAAGG 36 36 base pairs nucleic acidsingle linear 540 GUCUGUGCUG AUGAGGCCGA AAGGCCGAAA CACUCC 36 36 basepairs nucleic acid single linear 541 GGUCUGUCUG AUGAGGCCGA AAGGCCGAAAACACUC 36 36 base pairs nucleic acid single linear 542 GUCCACACUGAUGAGGCCGA AAGGCCGAAA UGCCAG 36 36 base pairs nucleic acid single linear543 AGUUCCCCUG AUGAGGCCGA AAGGCCGAAA CCGAAG 36 36 base pairs nucleicacid single linear 544 AAACUCUCUG AUGAGGCCGA AAGGCCGAAA GUUGUC 36 36base pairs nucleic acid single linear 545 CUGCUGACUG AUGAGGCCGAAAGGCCGAAA CUCUGA 36 36 base pairs nucleic acid single linear 546GCUGCUGCUG AUGAGGCCGA AAGGCCGAAA ACUCUG 36 36 base pairs nucleic acidsingle linear 547 AGCUGCUCUG AUGAGGCCGA AAGGCCGAAA AACUCU 36 36 basepairs nucleic acid single linear 548 ACACAGGCUG AUGAGGCCGA AAGGCCGAAAUGCACC 36 36 base pairs nucleic acid single linear 549 UUCAGGGCUGAUGAGGCCGA AAGGCCGAAA CUCCAU 36 36 base pairs nucleic acid single linear550 CGAGUUACUG AUGAGGCCGA AAGGCCGAAA GCUUCA 36 36 base pairs nucleicacid single linear 551 GGCGAGUCUG AUGAGGCCGA AAGGCCGAAA UAGCUU 36 36base pairs nucleic acid single linear 552 ACCAGGCCUG AUGAGGCCGAAAGGCCGAAA GUUAUA 36 36 base pairs nucleic acid single linear 553CCCUCUCCUG AUGAGGCCGA AAGGCCGAAA GGAGAG 36 36 base pairs nucleic acidsingle linear 554 GGGGCAGCUG AUGAGGCCGA AAGGCCGAAA GCUGGG 36 36 basepairs nucleic acid single linear 555 CCUACCGCUG AUGAGGCCGA AAGGCCGAAAGCAGGA 36 36 base pairs nucleic acid single linear 556 CAUUGGGCUGAUGAGGCCGA AAGGCCGAAA GCCCCG 36 36 base pairs nucleic acid single linear557 CUGGGCACUG AUGAGGCCGA AAGGCCGAAA GGUCAG 36 36 base pairs nucleicacid single linear 558 CACCUGGCUG AUGAGGCCGA AAGGCCGAAA GCAGAG 36 36base pairs nucleic acid single linear 559 UCACCUGCUG AUGAGGCCGAAAGGCCGAAA AGCAGA 36 36 base pairs nucleic acid single linear 560ACCUCCGCUG AUGAGGCCGA AAGGCCGAAA AGCGAG 36 36 base pairs nucleic acidsingle linear 561 GGAGGAGCUG AUGAGGCCGA AAGGCCGAAA GUCUUC 36 36 basepairs nucleic acid single linear 562 UGGAGGACUG AUGAGGCCGA AAGGCCGAAAAGUCUU 36 36 base pairs nucleic acid single linear 563 AAUGGAGCUGAUGAGGCCGA AAGGCCGAAA GAAGUC 36 36 base pairs nucleic acid single linear564 CGCAAUGCUG AUGAGGCCGA AAGGCCGAAA GGAGAA 36 36 base pairs nucleicacid single linear 565 UGUCCGCCUG AUGAGGCCGA AAGGCCGAAA UGGAGG 36 36base pairs nucleic acid single linear 566 AGCAGAGCUG AUGAGGCCGAAAGGCCGAAA GUCCAU 36 36 base pairs nucleic acid single linear 567GAGCAGACUG AUGAGGCCGA AAGGCCGAAA AGUCCA 36 36 base pairs nucleic acidsingle linear 568 AAGAGCACUG AUGAGGCCGA AAGGCCGAAA GAAGUC 36 36 basepairs nucleic acid single linear 569 CUGAUCUCUG AUGAGGCCGA AAGGCCGAAACUCAAA 36 36 base pairs nucleic acid single linear 570 AGGAGCUCUGAUGAGGCCGA AAGGCCGAAA UCUGAC 36 36 base pairs nucleic acid single linear571 ACCUUAGCUG AUGAGGCCGA AAGGCCGAAA GCUGAU 36 36 base pairs nucleicacid single linear 572 AGCACCUCUG AUGAGGCCGA AAGGCCGAAA GGAGCU 36 36base pairs nucleic acid single linear 573 CUCUUGGCUG AUGAGGCCGAAAGGCCGAAA GCACUG 36 36 base pairs nucleic acid single linear 574UACAGACCUG AUGAGGCCGA AAGGCCGAAA GCCAUU 36 36 base pairs nucleic acidsingle linear 575 CACUACACUG AUGAGGCCGA AAGGCCGAAA CGAGCC 36 36 basepairs nucleic acid single linear 576 CGUGCACCUG AUGAGGCCGA AAGGCCGAAACAGACG 36 36 base pairs nucleic acid single linear 577 GAGGGGGCUGAUGAGGCCGA AAGGCCGAAA CAGUUC 36 36 base pairs nucleic acid single linear578 UGAGGGGCUG AUGAGGCCGA AAGGCCGAAA ACAGUU 36 36 base pairs nucleicacid single linear 579 GGAAGAUCUG AUGAGGCCGA AAGGCCGAAA GGGGGA 36 36base pairs nucleic acid single linear 580 CCGGGAACUG AUGAGGCCGAAAGGCCGAAA UGAGGG 36 36 base pairs nucleic acid single linear 581UGCCGGGCUG AUGAGGCCGA AAGGCCGAAA GAUGAG 36 36 base pairs nucleic acidsingle linear 582 CUGCCGGCUG AUGAGGCCGA AAGGCCGAAA AGAUGA 36 36 basepairs nucleic acid single linear 583 GGGGCCACUG AUGAGGCCGA AAGGCCGAAAGGCCUG 36 36 base pairs nucleic acid single linear 584 CUCCACACUGAUGAGGCCGA AAGGCCGAAA GGGGCC 36 36 base pairs nucleic acid single linear585 GCUCAAUCUG AUGAGGCCGA AAGGCCGAAA UCUCCA 36 36 base pairs nucleicacid single linear 586 GCUGCUCCUG AUGAGGCCGA AAGGCCGAAA UGAUCU 36 36base pairs nucleic acid single linear 587 GUAGCGGCUG AUGAGGCCGAAAGGCCGAAA GCGCAU 36 36 base pairs nucleic acid single linear 588UGUAGCGCUG AUGAGGCCGA AAGGCCGAAA AGCGCA 36 36 base pairs nucleic acidsingle linear 589 GCACUUGCUG AUGAGGCCGA AAGGCCGAAA GCGGAA 36 36 basepairs nucleic acid single linear 590 GCCCGCGCUG AUGAGGCCGA AAGGCCGAAAGCGCCC 36 36 base pairs nucleic acid single linear 591 CGCCUGGCUGAUGAGGCCGA AAGGCCGAAA UGCUGC 36 36 base pairs nucleic acid single linear592 UUGGUGGCUG AUGAGGCCGA AAGGCCGAAA UCUGUG 36 36 base pairs nucleicacid single linear 593 UGAUCUUCUG AUGAGGCCGA AAGGCCGAAA UGGUGG 36 36base pairs nucleic acid single linear 594 AGCCAUUCUG AUGAGGCCGAAAGGCCGAAA UCUUGA 36 36 base pairs nucleic acid single linear 595UCCUGUGCUG AUGAGGCCGA AAGGCCGAAA GCCAUU 36 36 base pairs nucleic acidsingle linear 596 CCAGGGACUG AUGAGGCCGA AAGGCCGAAA UGCGCA 36 36 basepairs nucleic acid single linear 597 GACCAGGCUG AUGAGGCCGA AAGGCCGAAAGAUGCG 36 36 base pairs nucleic acid single linear 598 CCUUGGUCUGAUGAGGCCGA AAGGCCGAAA CCAGGG 36 36 base pairs nucleic acid single linear599 CGGUGAGCUG AUGAGGCCGA AAGGCCGAAA GGGUCC 36 36 base pairs nucleicacid single linear 600 GGCCGGUCUG AUGAGGCCGA AAGGCCGAAA GGAGGG 36 36base pairs nucleic acid single linear 601 UGGGGGUCUG AUGAGGCCGAAAGGCCGAAA GGCCGG 36 36 base pairs nucleic acid single linear 602UUCCUACCUG AUGAGGCCGA AAGGCCGAAA GCUCGU 36 36 base pairs nucleic acidsingle linear 603 CCUUUCCCUG AUGAGGCCGA AAGGCCGAAA CAAGCU 36 36 basepairs nucleic acid single linear 604 CUCAUAGCUG AUGAGGCCGA AAGGCCGAAAGCCAUC 36 36 base pairs nucleic acid single linear 605 CCUCAUACUGAUGAGGCCGA AAGGCCGAAA AGCCAU 36 36 base pairs nucleic acid single linear606 AGCCUCACUG AUGAGGCCGA AAGGCCGAAA GAAGCC 36 36 base pairs nucleicacid single linear 607 CCGGGCACUG AUGAGGCCGA AAGGCCGAAA GCUCAG 36 36base pairs nucleic acid single linear 608 AACUGUGCUG AUGAGGCCGAAAGGCCGAAA UGCAGC 36 36 base pairs nucleic acid single linear 609UUCUGGACUG AUGAGGCCGA AAGGCCGAAA CUGUGG 36 36 base pairs nucleic acidsingle linear 610 GUUCUGGCUG AUGAGGCCGA AAGGCCGAAA ACUGUG 36 36 basepairs nucleic acid single linear 611 GGUUCUGCUG AUGAGGCCGA AAGGCCGAAAAACUGU 36 36 base pairs nucleic acid single linear 612 CACACUGCUGAUGAGGCCGA AAGGCCGAAA UUCCCA 36 36 base pairs nucleic acid single linear613 UGACUGACUG AUGAGGCCGA AAGGCCGAAA GCCUGC 36 36 base pairs nucleicacid single linear 614 GCUGACUCUG AUGAGGCCGA AAGGCCGAAA UAGCCU 36 36base pairs nucleic acid single linear 615 AUGCGCUCUG AUGAGGCCGAAAGGCCGAAA CUGAUA 36 36 base pairs nucleic acid single linear 616UGGUCUGCUG AUGAGGCCGA AAGGCCGAAA UGCGCU 36 36 base pairs nucleic acidsingle linear 617 AACUUGGCUG AUGAGGCCGA AAGGCCGAAA GGGGUU 36 36 basepairs nucleic acid single linear 618 GAACUUGCUG AUGAGGCCGA AAGGCCGAAAAGGGGU 36 36 base pairs nucleic acid single linear 619 CUAUAGGCUGAUGAGGCCGA AAGGCCGAAA CUUGGA 36 36 base pairs nucleic acid single linear620 UCUAUAGCUG AUGAGGCCGA AAGGCCGAAA ACUUGG 36 36 base pairs nucleicacid single linear 621 UCUUCUACUG AUGAGGCCGA AAGGCCGAAA GGAACU 36 36base pairs nucleic acid single linear 622 GCUCUUCCUG AUGAGGCCGAAAGGCCGAAA UAGGAA 36 36 base pairs nucleic acid single linear 623CAGGUCGCUG AUGAGGCCGA AAGGCCGAAA GUCCCC 36 36 base pairs nucleic acidsingle linear 624 GGAAGCACUG AUGAGGCCGA AAGGCCGAAA GCCGCA 36 36 basepairs nucleic acid single linear 625 CACCUGGCUG AUGAGGCCGA AAGGCCGAAAGCAGAG 36 36 base pairs nucleic acid single linear 626 UCACCUGCUGAUGAGGCCGA AAGGCCGAAA AGCAGA 36 36 base pairs nucleic acid single linear627 CCUGCCUCUG AUGAGGCCGA AAGGCCGAAA UGGGUC 36 36 base pairs nucleicacid single linear 628 GCAGGCGCUG AUGAGGCCGA AAGGCCGAAA GGGGCC 36 36base pairs nucleic acid single linear 629 GAGGAAGCUG AUGAGGCCGAAAGGCCGAAA CAGGCG 36 36 base pairs nucleic acid single linear 630GAUGAGGCUG AUGAGGCCGA AAGGCCGAAA GGACAG 36 36 base pairs nucleic acidsingle linear 631 GGAUGAGCUG AUGAGGCCGA AAGGCCGAAA AGGACA 36 36 basepairs nucleic acid single linear 632 AUGGGAUCUG AUGAGGCCGA AAGGCCGAAAGGAAGG 36 36 base pairs nucleic acid single linear 633 AAGAUGGCUGAUGAGGCCGA AAGGCCGAAA UGAGGA 36 36 base pairs nucleic acid single linear634 UGUCAAACUG AUGAGGCCGA AAGGCCGAAA UGGGAU 36 36 base pairs nucleicacid single linear 635 AUUGUCACUG AUGAGGCCGA AAGGCCGAAA GAUGGG 36 36base pairs nucleic acid single linear 636 GAUUGUCCUG AUGAGGCCGAAAGGCCGAAA AGAUGG 36 36 base pairs nucleic acid single linear 637GGGGCACCUG AUGAGGCCGA AAGGCCGAAA UUGUCA 36 36 base pairs nucleic acidsingle linear 638 AGAUCUUCUG AUGAGGCCGA AAGGCCGAAA GCUCGG 36 36 basepairs nucleic acid single linear 639 CUCGGCACUG AUGAGGCCGA AAGGCCGAAAUCUUGA 36 36 base pairs nucleic acid single linear 640 GCUGCCACUGAUGAGGCCGA AAGGCCGAAA GUUUCG 36 36 base pairs nucleic acid single linear641 CCCCACCCUG AUGAGGCCGA AAGGCCGAAA GGCAGC 36 36 base pairs nucleicacid single linear 642 GUAGGAACUG AUGAGGCCGA AAGGCCGAAA UCUCAU 36 36base pairs nucleic acid single linear 643 CAGUAGGCUG AUGAGGCCGAAAGGCCGAAA GAUCUC 36 36 base pairs nucleic acid single linear 644ACAGUAGCUG AUGAGGCCGA AAGGCCGAAA AGAUCU 36 36 base pairs nucleic acidsingle linear 645 CACACAGCUG AUGAGGCCGA AAGGCCGAAA GGAAGA 36 36 basepairs nucleic acid single linear 646 ACACCUCCUG AUGAGGCCGA AAGGCCGAAAUGUCCU 36 36 base pairs nucleic acid single linear 647 CGUGAAACUGAUGAGGCCGA AAGGCCGAAA CACCUC 36 36 base pairs nucleic acid single linear648 CCCGUGACUG AUGAGGCCGA AAGGCCGAAA UACACC 36 36 base pairs nucleicacid single linear 649 UCCCGUGCUG AUGAGGCCGA AAGGCCGAAA AUACAC 36 36base pairs nucleic acid single linear 650 GUCCCGUCUG AUGAGGCCGAAAGGCCGAAA AAUACA 36 36 base pairs nucleic acid single linear 651CGAAAAGCUG AUGAGGCCGA AAGGCCGAAA GCCUCG 36 36 base pairs nucleic acidsingle linear 652 UUGCGAACUG AUGAGGCCGA AAGGCCGAAA GGAGCC 36 36 basepairs nucleic acid single linear 653 CUUGCGACUG AUGAGGCCGA AAGGCCGAAAAGGAGC 36 36 base pairs nucleic acid single linear 654 GCUUGCGCUGAUGAGGCCGA AAGGCCGAAA AAGGAG 36 36 base pairs nucleic acid single linear655 AGCUUGCCUG AUGAGGCCGA AAGGCCGAAA AAAGGA 36 36 base pairs nucleicacid single linear 656 GGAACACCUG AUGAGGCCGA AAGGCCGAAA UGGCCA 36 36base pairs nucleic acid single linear 657 GGUCCGGCUG AUGAGGCCGAAAGGCCGAAA CACAAU 36 36 base pairs nucleic acid single linear 658GGGUCCGCUG AUGAGGCCGA AAGGCCGAAA ACACAA 36 36 base pairs nucleic acidsingle linear 659 GCGUAGGCUG AUGAGGCCGA AAGGCCGAAA GGGGUC 36 36 basepairs nucleic acid single linear 660 GUCUGCGCUG AUGAGGCCGA AAGGCCGAAAGGGAGG 36 36 base pairs nucleic acid single linear 661 CGCACAGCUGAUGAGGCCGA AAGGCCGAAA GCCUGC 36 36 base pairs nucleic acid single linear662 GCAUGGACUG AUGAGGCCGA AAGGCCGAAA CACGCA 36 36 base pairs nucleicacid single linear 663 CUGCAUGCUG AUGAGGCCGA AAGGCCGAAA GACACG 36 36base pairs nucleic acid single linear 664 CGGUCGGCUG AUGAGGCCGAAAGGCCGAAA GGCCGC 36 36 base pairs nucleic acid single linear 665CCGGUCGCUG AUGAGGCCGA AAGGCCGAAA AGGCCG 36 36 base pairs nucleic acidsingle linear 666 GCUCACUCUG AUGAGGCCGA AAGGCCGAAA GCUCCC 36 36 basepairs nucleic acid single linear 667 GUACUGGCUG AUGAGGCCGA AAGGCCGAAAUUCCAU 36 36 base pairs nucleic acid single linear 668 GGUACUGCUGAUGAGGCCGA AAGGCCGAAA AUUCCA 36 36 base pairs nucleic acid single linear669 UGGCAGGCUG AUGAGGCCGA AAGGCCGAAA CUGGAA 36 36 base pairs nucleicacid single linear 670 UCGUCUGCUG AUGAGGCCGA AAGGCCGAAA UCUGGC 36 36base pairs nucleic acid single linear 671 CGGUGACCUG AUGAGGCCGAAAGGCCGAAA UCGUCU 36 36 base pairs nucleic acid single linear 672AUCCGGUCUG AUGAGGCCGA AAGGCCGAAA CGAUCG 36 36 base pairs nucleic acidsingle linear 673 UCUCCUCCUG AUGAGGCCGA AAGGCCGAAA UCCGGU 36 36 basepairs nucleic acid single linear 674 GUCCUUUCUG AUGAGGCCGA AAGGCCGAAACGUUUC 36 36 base pairs nucleic acid single linear 675 GGUCUCACUGAUGAGGCCGA AAGGCCGAAA UGUCCU 36 36 base pairs nucleic acid single linear676 GCUCUUGCUG AUGAGGCCGA AAGGCCGAAA GGUCUC 36 36 base pairs nucleicacid single linear 677 UGCUCUUCUG AUGAGGCCGA AAGGCCGAAA AGGUCU 36 36base pairs nucleic acid single linear 678 UCUUCAUCUG AUGAGGCCGAAAGGCCGAAA UGCUCU 36 36 base pairs nucleic acid single linear 679CUGAAAGCUG AUGAGGCCGA AAGGCCGAAA CUCUUC 36 36 base pairs nucleic acidsingle linear 680 CCGCUGACUG AUGAGGCCGA AAGGCCGAAA GGACUC 36 36 basepairs nucleic acid single linear 681 UCCGCUGCUG AUGAGGCCGA AAGGCCGAAAAGGACU 36 36 base pairs nucleic acid single linear 682 GUCCGCUCUGAUGAGGCCGA AAGGCCGAAA AAGGAC 36 36 base pairs nucleic acid single linear683 CGAGGUGCUG AUGAGGCCGA AAGGCCGAAA GGCCGG 36 36 base pairs nucleicacid single linear 684 AUGCGUCCUG AUGAGGCCGA AAGGCCGAAA GGUGGA 36 36base pairs nucleic acid single linear 685 GCACAGCCUG AUGAGGCCGAAAGGCCGAAA UGCGUC 36 36 base pairs nucleic acid single linear 686CUGCGGGCUG AUGAGGCCGA AAGGCCGAAA GGCACA 36 36 base pairs nucleic acidsingle linear 687 GCUGCGGCUG AUGAGGCCGA AAGGCCGAAA AGGCAC 36 36 basepairs nucleic acid single linear 688 AGAAGCUCUG AUGAGGCCGA AAGGCCGAAAGCUGCG 36 36 base pairs nucleic acid single linear 689 GGGACAGCUGAUGAGGCCGA AAGGCCGAAA GCUGAG 36 36 base pairs nucleic acid single linear690 GGGGACACUG AUGAGGCCGA AAGGCCGAAA AGCUGA 36 36 base pairs nucleicacid single linear 691 GCUUGGGCUG AUGAGGCCGA AAGGCCGAAA CAGAAG 36 36base pairs nucleic acid single linear 692 AAAGGGACUG AUGAGGCCGAAAGGCCGAAA GGGCUG 36 36 base pairs nucleic acid single linear 693GUAAAGGCUG AUGAGGCCGA AAGGCCGAAA UAGGGC 36 36 base pairs nucleic acidsingle linear 694 UGACGUACUG AUGAGGCCGA AAGGCCGAAA GGGAUA 36 36 basepairs nucleic acid single linear 695 AUGACGUCUG AUGAGGCCGA AAGGCCGAAAAGGGAU 36 36 base pairs nucleic acid single linear 696 GAUGACGCUGAUGAGGCCGA AAGGCCGAAA AAGGGA 36 36 base pairs nucleic acid single linear697 CAGGGAUCUG AUGAGGCCGA AAGGCCGAAA CGUAAA 36 36 base pairs nucleicacid single linear 698 GCUCAGGCUG AUGAGGCCGA AAGGCCGAAA UGACGU 36 36base pairs nucleic acid single linear 699 CAUAGUUCUG AUGAGGCCGAAAGGCCGAAA UGGUGC 36 36 base pairs nucleic acid single linear 700CUCAUCACUG AUGAGGCCGA AAGGCCGAAA GUUGAU 36 36 base pairs nucleic acidsingle linear 701 GGUGGGACUG AUGAGGCCGA AAGGCCGAAA CUCAUC 36 36 basepairs nucleic acid single linear 702 UGGUGGGCUG AUGAGGCCGA AAGGCCGAAAACUCAU 36 36 base pairs nucleic acid single linear 703 AUGGUGGCUGAUGAGGCCGA AAGGCCGAAA AACUCA 36 36 base pairs nucleic acid single linear704 AGAAGGACUG AUGAGGCCGA AAGGCCGAAA CACCAU 36 36 base pairs nucleicacid single linear 705 CAGAAGGCUG AUGAGGCCGA AAGGCCGAAA ACACCA 36 36base pairs nucleic acid single linear 706 CCAGAAGCUG AUGAGGCCGAAAGGCCGAAA AACACC 36 36 base pairs nucleic acid single linear 707UGCCCAGCUG AUGAGGCCGA AAGGCCGAAA GGAAAC 36 36 base pairs nucleic acidsingle linear 708 CUGCCCACUG AUGAGGCCGA AAGGCCGAAA AGGAAA 36 36 basepairs nucleic acid single linear 709 CCUGGCUCUG AUGAGGCCGA AAGGCCGAAAUCUGCC 36 36 base pairs nucleic acid single linear 710 CAAGGCCCUGAUGAGGCCGA AAGGCCGAAA GGCCUG 36 36 base pairs nucleic acid single linear711 CGGGGCCCUG AUGAGGCCGA AAGGCCGAAA GGCCGA 36 36 base pairs nucleicacid single linear 712 ACUUGGGCUG AUGAGGCCGA AAGGCCGAAA GGGGCC 36 36base pairs nucleic acid single linear 713 GGGGCAGCUG AUGAGGCCGAAAGGCCGAAA CUUGGG 36 36 base pairs nucleic acid single linear 714GGGGCUGCUG AUGAGGCCGA AAGGCCGAAA GCCUGG 36 36 base pairs nucleic acidsingle linear 715 AUGGCUGCUG AUGAGGCCGA AAGGCCGAAA GCAGGG 36 36 basepairs nucleic acid single linear 716 GAGCUGACUG AUGAGGCCGA AAGGCCGAAACCAUGG 36 36 base pairs nucleic acid single linear 717 CAGAGCUCUGAUGAGGCCGA AAGGCCGAAA UACCAU 36 36 base pairs nucleic acid single linear718 UGGGCCACUG AUGAGGCCGA AAGGCCGAAA GCUGAU 36 36 base pairs nucleicacid single linear 719 GGACUGGCUG AUGAGGCCGA AAGGCCGAAA CAGGGG 36 36base pairs nucleic acid single linear 720 GGGCUAGCUG AUGAGGCCGAAAGGCCGAAA CUGGGA 36 36 base pairs nucleic acid single linear 721CUGGGGCCUG AUGAGGCCGA AAGGCCGAAA GGACUG 36 36 base pairs nucleic acidsingle linear 722 GCCUGAGCUG AUGAGGCCGA AAGGCCGAAA GGGCCU 36 36 basepairs nucleic acid single linear 723 ACAGCCUCUG AUGAGGCCGA AAGGCCGAAAGGAGGG 36 36 base pairs nucleic acid single linear 724 GGCCUCUCUGAUGAGGCCGA AAGGCCGAAA CAGCGU 36 36 base pairs nucleic acid single linear725 AUCAUCACUG AUGAGGCCGA AAGGCCGAAA CUGCAG 36 36 base pairs nucleicacid single linear 726 CAUCAUCCUG AUGAGGCCGA AAGGCCGAAA ACUGCA 36 36base pairs nucleic acid single linear 727 GCCAAGCCUG AUGAGGCCGAAAGGCCGAAA GGCCCC 36 36 base pairs nucleic acid single linear 728UGUUGCCCUG AUGAGGCCGA AAGGCCGAAA GCAAGG 36 36 base pairs nucleic acidsingle linear 729 GUCUGUGCUG AUGAGGCCGA AAGGCCGAAA CACAGC 36 36 basepairs nucleic acid single linear 730 GGUCUGUCUG AUGAGGCCGA AAGGCCGAAAACACAG 36 36 base pairs nucleic acid single linear 731 GUCGACGCUGAUGAGGCCGA AAGGCCGAAA UGCCAG 36 36 base pairs nucleic acid single linear732 AGUUGUCCUG AUGAGGCCGA AAGGCCGAAA CGGAUG 36 36 base pairs nucleicacid single linear 733 AAACUCGCUG AUGAGGCCGA AAGGCCGAAA GUUGUC 36 36base pairs nucleic acid single linear 734 CUGCUGACUG AUGAGGCCGAAAGGCCGAAA CUCGGA 36 36 base pairs nucleic acid single linear 735GCUGCUGCUG AUGAGGCCGA AAGGCCGAAA ACUCGG 36 36 base pairs nucleic acidsingle linear 736 AGCUGCUCUG AUGAGGCCGA AAGGCCGAAA AACUCG 36 36 basepairs nucleic acid single linear 737 CCACAGGCUG AUGAGGCCGA AAGGCCGAAAUGCCCU 36 36 base pairs nucleic acid single linear 738 CUCAGGGCUGAUGAGGCCGA AAGGCCGAAA CUCCAU 36 36 base pairs nucleic acid single linear739 CGAGUUACUG AUGAGGCCGA AAGGCCGAAA GCCUCA 36 36 base pairs nucleicacid single linear 740 GGCGAGUCUG AUGAGGCCGA AAGGCCGAAA UAGCCU 36 36base pairs nucleic acid single linear 741 ACUAGGCCUG AUGAGGCCGAAAGGCCGAAA GUUAUA 36 36 base pairs nucleic acid single linear 742CUGUCACCUG AUGAGGCCGA AAGGCCGAAA GGCGAG 36 36 base pairs nucleic acidsingle linear 743 GGAGCAGCUG AUGAGGCCGA AAGGCCGAAA GCUGGG 36 36 basepairs nucleic acid single linear 744 CCCAGUGCUG AUGAGGCCGA AAGGCCGAAAGCAGGA 36 36 base pairs nucleic acid single linear 745 CAUUGGGCUGAUGAGGCCGA AAGGCCGAAA GCCCCG 36 36 base pairs nucleic acid single linear746 CUGAAAGCUG AUGAGGCCGA AAGGCCGAAA GGCCAU 36 36 base pairs nucleicacid single linear 747 CUCCUGACUG AUGAGGCCGA AAGGCCGAAA GGAGGC 36 36base pairs nucleic acid single linear 748 UCUCCUGCUG AUGAGGCCGAAAGGCCGAAA AGGAGG 36 36 base pairs nucleic acid single linear 749AUCUCCUCUG AUGAGGCCGA AAGGCCGAAA AAGGAG 36 36 base pairs nucleic acidsingle linear 750 GGAGGAGCUG AUGAGGCCGA AAGGCCGAAA GUCUUC 36 36 basepairs nucleic acid single linear 751 UGGAGGACUG AUGAGGCCGA AAGGCCGAAAAGUCUU 36 36 base pairs nucleic acid single linear 752 AAUGGAGCUGAUGAGGCCGA AAGGCCGAAA GAAGUC 36 36 base pairs nucleic acid single linear753 CGCAAUGCUG AUGAGGCCGA AAGGCCGAAA GGAGAA 36 36 base pairs nucleicacid single linear 754 UGUCCGCCUG AUGAGGCCGA AAGGCCGAAA UGGAGG 36 36base pairs nucleic acid single linear 755 GGCUGAGCUG AUGAGGCCGAAAGGCCGAAA GUCCAU 36 36 base pairs nucleic acid single linear 756GGGCUGACUG AUGAGGCCGA AAGGCCGAAA AGUCCA 36 36 base pairs nucleic acidsingle linear 757 CAGGGCUCUG AUGAGGCCGA AAGGCCGAAA GAAGUC 36 36 basepairs nucleic acid single linear 758 CUGAUCUCUG AUGAGGCCGA AAGGCCGAAACUCAGC 36 36 base pairs nucleic acid single linear 759 AGGAGCUCUGAUGAGGCCGA AAGGCCGAAA UCUGAC 36 36 base pairs nucleic acid single linear760 CCCUUAGCUG AUGAGGCCGA AAGGCCGAAA GCUGAU 36 36 base pairs nucleicacid single linear 761 ACCCCCUCUG AUGAGGCCGA AAGGCCGAAA GGAGCU 36 36base pairs nucleic acid single linear 762 CUCUGGGCUG AUGAGGCCGAAAGGCCGAAA GGGCAG 36 52 base pairs nucleic acid single linear 763UGAGGGGGAG AAGUUCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 764 GCUGCUUGAG AAGCUCACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 765GCCAUCCCAG AAGUCCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 766 GUUCUGGAAG AAGUGGACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 767GAAGGACAAG AAGCAGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 768 UUGAGCUCAG AAGUGUACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 769CCCACCGAAG AAGCUGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 770 AGGCUGGGAG AAGCGUACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 771GGUCGGAAAG AAGCCGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 772 UGACGAUCAG AAGUAUACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 773GUCGGUGGAG AAGCUGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 774 GGCCGGGGAG AAGUGGACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 775CAUCAUCAAG AAGCAGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 776 ACAGCUGGAG AAGUGCACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 777GAUGCCAGAG AAGUGAACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 16 basepairs nucleic acid single linear 778 GAACUGUUCC CCCUCA 16 16 base pairsnucleic acid single linear 779 GAGCAGCCCA AGCAGC 16 16 base pairsnucleic acid single linear 780 GGACUGCCGG GAUGGC 16 16 base pairsnucleic acid single linear 781 CCACAGUUUC CAGAAC 16 16 base pairsnucleic acid single linear 782 CUGCCGCCUG UCCUUC 16 16 base pairsnucleic acid single linear 783 ACACUGCCGA GCUCAA 16 16 base pairsnucleic acid single linear 784 CAGCUGCCUC GGUGGG 16 16 base pairsnucleic acid single linear 785 ACGCAGACCC CAGCCU 16 16 base pairsnucleic acid single linear 786 CGGCGGCCUU CCGACC 16 16 base pairsnucleic acid single linear 787 AUACAGACGA UCGUCA 16 16 base pairsnucleic acid single linear 788 CAGCGGACCC ACCGAC 16 16 base pairsnucleic acid single linear 789 CCACCGACCC CCGGCC 16 16 base pairsnucleic acid single linear 790 CUGCAGUUUG AUGAUG 16 16 base pairsnucleic acid single linear 791 GCACAGACCC AGCUGU 16 16 base pairsnucleic acid single linear 792 UCACAGACCU GGCAUC 16 52 base pairsnucleic acid single linear 793 GUUGCUUCAG AAGUUCACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 794GAGAUUCGAG AAGUUCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 795 GCCAUCCCAG AAGUCCACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 796GGGCAGAGAG AAGCCUACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 797 UUGAGCUCAG AAGUGUACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 798CCCACCGAAG AAGCUCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 799 AGGCUGGGAG AAGCGUACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 800GAUCAGAAAG AAGCCGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 801 AGGUGUAGAG AAGCGGACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 802GGGCAGAGAG AAGUGCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 803 GGGCUUCCAG AAGCGUACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 804CAGCAUCAAG AAGCAGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 805 ACUCCUGGAG AAGUGCACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 806GAUGCCAGAG AAGUGAACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 807 AAGUCGGGAG AAGCUGACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 808UGGCUCCAAG AAGUCCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 809 UGGUGUCGAG AAGCACACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 810AUUCUGAAAG AAGCCAACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 basepairs nucleic acid single linear 811 UCAGUAAAAG AAGUCUACCA GAGAAACACACGUUGUGGUA CAUUACCUGG UA 52 16 base pairs nucleic acid single linear 812GAACAGCCGA AGCAAC 16 16 base pairs nucleic acid single linear 813GAACAGUUCG AAUCUC 16 16 base pairs nucleic acid single linear 814GGACUGCCGG GAUGGC 16 16 base pairs nucleic acid single linear 815AGGCUGACCU CUGCCC 16 16 base pairs nucleic acid single linear 816ACACUGCCGA GCUCAA 16 16 base pairs nucleic acid single linear 817GAGCUGCCUC GGUGGG 16 16 base pairs nucleic acid single linear 818ACGCCGACCC CAGCCU 16 16 base pairs nucleic acid single linear 819CGGCGGCCUU CUGAUC 16 16 base pairs nucleic acid single linear 820CCGCAGCCCU ACACCU 16 16 base pairs nucleic acid single linear 821GCACCGUCCU CUGCCC 16 16 base pairs nucleic acid single linear 822ACGCUGUCGG AAGCCC 16 16 base pairs nucleic acid single linear 823CUGCAGUUUG AUGCUG 16 16 base pairs nucleic acid single linear 824GCACAGACCC AGGAGU 16 16 base pairs nucleic acid single linear 825UCACAGACCU GGCAUC 16 16 base pairs nucleic acid single linear 826CAGCUGCCCC CGACUU 16 16 base pairs nucleic acid single linear 827GGACAGACUG GAGCCA 16 16 base pairs nucleic acid single linear 828GUGCUGCCCG ACACCA 16 16 base pairs nucleic acid single linear 829UGGCCGCCUU CAGAAU 16 16 base pairs nucleic acid single linear 830AGACAGCCUU UACUGA 16

1. An enzymatic RNA molecule which cleaves rel A mRNA.
 2. An enzymaticRNA molecule of claim 1, the binding arms of which contain sequencescomplementary to the sequences defined in Table II.
 3. The enzymatic RNAmolecule of claim 1, the binding arms of which contain sequencescomplementary to the sequences defined in any one of Tables III, andIV-VII
 4. The enzymatic RNA molecule of claim 1, 2, or 3, wherein saidRNA molecule is in a hammerhead motif.
 5. The enzymatic RNA molecule ofclaim 1, 2, or 3, wherein said RNA molecule is in a hairpin, hepatitisdelta virus, group 1 intron, VS RNA or RNAseP RNA motif.
 6. Theenzymatic RNA molecule of claim 6, wherein said ribozyme comprisesbetween 12 and 100 bases complementary to said mRNA.
 7. The enzymaticRNA molecule of claim 6, wherein said ribozyme comprises between 14 and24 bases complementary to said mRNA.
 8. Enzymatic RNA moleculeconsisting essentially of any sequence selected from the group of thoseshown in Tables IV, V, VI, and VII.
 9. A mammalian cell including anenzymatic RNA molecule of claim 1, 2, or
 3. 10. The cell of claim 8,wherein said cell is a human cell.
 11. An expression vector includingnucleic acid encoding an enzymatic RNA molecule or multiple enzymaticmolecules of claim 1, 2, or 3 in a manner which allows expression ofthat enzymatic RNA molecule(s) within a mammalian cell.
 12. A mammaliancell including an expression vector of claim
 11. 13. The cell of claim13, wherein said cell is a human cell.
 14. A method for treatment of acondition related to the level of NF-κB activity by administering to apatient an enzymatic nucleic acid molecule of claim 1, 2, or 3,
 15. Amethod for treatment of a condition related to the level of NF-κBactivity by administering to a patient an expression vector of claim 11.16. The method of claim 14 or 15, wherein said patient is a human. 17.The method of claim 14 wherein said condition is selected from the groupconsisting of restenosis, rheumatoid arthritis, asthma, inflammatory orautoimmune disorders, and transplant rejection.
 18. The method of claim15 wherein said condition is selected from the group consisting ofrestenosis, rheumatoid arthritis, asthma, inflammatory or autoimmunedisorders, and transplant rejection.